insulin receptor

Summary

Summary: A cell surface receptor for INSULIN. It is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precusor protein. The receptor contains an intrinsic tyrosine kinase domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the LIVER; MUSCLE; and ADIPOSE TISSUE.

Top Publications

  1. ncbi Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
    R S Savkur
    Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA
    Nat Genet 29:40-7. 2001
  2. ncbi Insulin signalling and the regulation of glucose and lipid metabolism
    A R Saltiel
    Life Sciences Institute, Department of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA
    Nature 414:799-806. 2001
  3. ncbi Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
    Coleen T Murphy
    Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143 2200, USA
    Nature 424:277-83. 2003
  4. ncbi daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans
    K D Kimura
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 277:942-6. 1997
  5. ncbi An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control
    W Brogiolo
    Zoologisches Institut, Universitat Zurich, Winterthurerstrasse 190, CH 8057, Zurich, Switzerland
    Curr Biol 11:213-21. 2001
  6. ncbi Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease
    Antonino Belfiore
    Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Ospedale Garibaldi Nesima, 95122 Catania, Italy
    Endocr Rev 30:586-623. 2009
  7. ncbi Extended longevity in mice lacking the insulin receptor in adipose tissue
    Matthias Bluher
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA, 02215 USA
    Science 299:572-4. 2003
  8. ncbi A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance
    J C Bruning
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Cell 2:559-69. 1998
  9. ncbi Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling
    K Lin
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA
    Nat Genet 28:139-45. 2001
  10. ncbi Autophagy genes are essential for dauer development and life-span extension in C. elegans
    Alicia Melendez
    Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    Science 301:1387-91. 2003

Research Grants

  1. Ang II and Aldosterone Effects on Insulin Resistance in Cardiovascular Tissue
    JAMES RUSSELL SOWERS; Fiscal Year: 2013
  2. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2011
  3. INSULIN RECEPTORS AND THE GLUCOSE TRANSPORT SYSTEM
    JERROLD MICHAEL OLEFSKY; Fiscal Year: 2013
  4. Biology of IGFs in Bone
    Thomas L Clemens; Fiscal Year: 2013
  5. Pathogenesis of the Metabolic Syndrome
    W Timothy Garvey; Fiscal Year: 2013
  6. JNK exacerbates ischemia/reperfusion injury in hyperglycemic subjects.
    Keith A Webster; Fiscal Year: 2010
  7. PTEN TUMOR SUPPRESSOR AND SIGNAL TRANSDUCTION
    RAMON E PARSONS; Fiscal Year: 2012
  8. A2b Adenosine Receptor Regulation of Metabolic Disease and Inflammation
    Anna Eisenstein; Fiscal Year: 2013
  9. Atypical PKC Knockout Models: Effect on Glucose and Lipid Homeostasis
    Robert V Farese; Fiscal Year: 2013
  10. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2013

Detail Information

Publications364 found, 100 shown here

  1. ncbi Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
    R S Savkur
    Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA
    Nat Genet 29:40-7. 2001
    ..Here we demonstrate that alternative splicing of the insulin receptor (IR) pre-mRNA is aberrantly regulated in DM1 skeletal muscle tissue, resulting in predominant expression of ..
  2. ncbi Insulin signalling and the regulation of glucose and lipid metabolism
    A R Saltiel
    Life Sciences Institute, Department of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA
    Nature 414:799-806. 2001
    ..The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells...
  3. ncbi Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
    Coleen T Murphy
    Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143 2200, USA
    Nature 424:277-83. 2003
    ....
  4. ncbi daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans
    K D Kimura
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 277:942-6. 1997
    ..daf-2, a key gene in the genetic pathway that mediates this endocrine signaling, encodes an insulin receptor family member...
  5. ncbi An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control
    W Brogiolo
    Zoologisches Institut, Universitat Zurich, Winterthurerstrasse 190, CH 8057, Zurich, Switzerland
    Curr Biol 11:213-21. 2001
    ..in Drosophila have identified an evolutionarily conserved signaling pathway that regulates organismal size and that includes the Drosophila insulin receptor substrate homolog Chico, the lipid kinase PI(3)K (Dp110), DAkt1/dPKB, and dS6K.
  6. ncbi Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease
    Antonino Belfiore
    Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Ospedale Garibaldi Nesima, 95122 Catania, Italy
    Endocr Rev 30:586-623. 2009
    In mammals, the insulin receptor (IR) gene has acquired an additional exon, exon 11. This exon may be skipped in a developmental and tissue-specific manner...
  7. ncbi Extended longevity in mice lacking the insulin receptor in adipose tissue
    Matthias Bluher
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA, 02215 USA
    Science 299:572-4. 2003
    ..To further explore these associations with enhanced longevity, we studied mice with a fat-specific insulin receptor knockout (FIRKO)...
  8. ncbi A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance
    J C Bruning
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Cell 2:559-69. 1998
    ..muscle insulin resistance to the metabolic phenotype of diabetes, we used the Cre-loxP system to disrupt the insulin receptor gene in mouse skeletal muscle...
  9. ncbi Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling
    K Lin
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA
    Nat Genet 28:139-45. 2001
    ..Together these findings reveal unexpected complexity in the DAF-16-dependent pathways that regulate aging...
  10. ncbi Autophagy genes are essential for dauer development and life-span extension in C. elegans
    Alicia Melendez
    Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    Science 301:1387-91. 2003
    ..elegans orthologs of the yeast autophagy genes APG1, APG7, APG8, and AUT10. Thus, autophagy is a cellular pathway essential for dauer development and life-span extension in C. elegans...
  11. ncbi Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens
    Danielle A Garsin
    Department of Genetics, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 300:1921. 2003
  12. pmc daf-28 encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway
    Weiqing Li
    Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA
    Genes Dev 17:844-58. 2003
    ..These sensory inputs are coupled to the parallel DAF-2/insulin receptor-like and DAF-7/TGFbeta-like signaling pathways...
  13. ncbi Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4
    R Bohni
    Zoologisches Institut, Universitat Zurich, Switzerland
    Cell 97:865-75. 1999
    ..The similarities of the growth defects caused by mutations in chico and the insulin receptor gene in Drosophila and by perturbations of the insulin/IGF1 signaling pathway in vertebrates suggest that ..
  14. ncbi Regulation of aging and age-related disease by DAF-16 and heat-shock factor
    Ao Lin Hsu
    Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143 2200, USA
    Science 300:1142-5. 2003
    ..The small heat-shock proteins also delay the onset of polyglutamine-expansion protein aggregation, suggesting that these proteins couple the normal aging process to this type of age-related disease...
  15. pmc Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog
    S R Hubbard
    Department of Pharmacology and Skirball Institute of Biomolecular Medicine, 540 First Avenue, New York University Medical Center, New York, NY 10016, USA
    EMBO J 16:5572-81. 1997
    The crystal structure of the phosphorylated, activated form of the insulin receptor tyrosine kinase in complex with a peptide substrate and an ATP analog has been determined at 1.9 A resolution...
  16. ncbi Disruption of IRS-2 causes type 2 diabetes in mice
    D J Withers
    Howard Hughes Medical Institute, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 391:900-4. 1998
    ..Our results indicate that dysfunction of IRS-2 may contribute to the pathophysiology of human type 2 diabetes...
  17. ncbi Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved
    Giuseppe Pandini
    Istituto di Medicina Interna, Malattie Endocrine e del Metabolismo, University of Catania, Ospedale Garibaldi, 95123 Catania, Italy
    J Biol Chem 277:39684-95. 2002
    The insulin receptor (IR) and the insulin-like growth factor I receptor (IGF-IR) have a highly homologous structure, but different biological effects...
  18. pmc Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition
    Keertik Fulzele
    Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 142:309-19. 2010
    ..Here, we show that insulin receptor (IR) signaling in osteoblasts controls osteoblast development and osteocalcin expression by suppressing the ..
  19. ncbi Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans
    Norbert Stefan
    Clinical Diabetes and Nutrition Section, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA
    Diabetes 51:1884-8. 2002
    ..administration to rodents has been shown to increase insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and also increase whole-body insulin sensitivity...
  20. ncbi Phosphorylated insulin-like growth factor-i/insulin receptor is present in all breast cancer subtypes and is related to poor survival
    Jennifer H Law
    Department of Pediatrics, Laboratory for Oncogenomic Research, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Cancer Res 68:10238-46. 2008
    Drugs that target the insulin-like growth factor-I receptor (IGF-IR) and/or insulin receptor (IR) are currently under investigation for a variety of malignancies including breast cancer...
  21. ncbi Insulin signaling in health and disease
    Morris F White
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
    Science 302:1710-1. 2003
    ..Drugs that stimulate IRS2 (insulin receptor substrate protein 2) synthesis or signaling might be a good starting point...
  22. ncbi Insulin analogues differently activate insulin receptor isoforms and post-receptor signalling
    L Sciacca
    Endocrinology, Department of Internal and Specialistic Medicine, University of Catania, Garibaldi Nesima Hospital, Via Palermo 636, 95122 Catania, Italy
    Diabetologia 53:1743-53. 2010
    ..They activate cell signalling and biological responses via insulin receptor isoforms (IR-A and IR-B), each having specific characteristics for eliciting cell responses...
  23. ncbi Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer's disease indicate possible resistance to IGF-1 and insulin signalling
    Aileen M Moloney
    Department of Biochemistry, Biosciences Institute, University College Cork, Cork, Ireland
    Neurobiol Aging 31:224-43. 2010
    Insulin like growth factor-1 receptor (IGF-1R) and insulin receptor (IR) signalling control vital growth, survival and metabolic functions in the brain...
  24. ncbi A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function
    M Tatar
    Brown University, Providence, RI 02912, USA, University of Massachusetts, Amherst, MA 01003, USA
    Science 292:107-10. 2001
    ....
  25. ncbi Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans
    Malene Hansen
    Department of Biochemistry and Biophysics, University of California, 600 16th Street, San Francisco, CA 94158, USA
    Aging Cell 6:95-110. 2007
    ..Our findings link TOR, but not sir-2.1, to the longevity response induced by dietary restriction (DR) in C. elegans, and they suggest that neither TOR inhibition nor DR extends lifespan simply by reducing protein synthesis...
  26. pmc Tumor necrosis factor alpha inhibits signaling from the insulin receptor
    G S Hotamisligil
    Dana Farber Cancer Institute, Boston, MA 02115
    Proc Natl Acad Sci U S A 91:4854-8. 1994
    ..TNF-alpha treatment causes a moderate decrease in the insulin-stimulated autophosphorylation of the insulin receptor (IR) and a dramatic decrease in the phosphorylation of IR substrate 1, the major substrate of the IR in vivo...
  27. pmc Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy
    Danielle B Ulanet
    Department of Biochemistry and Biophysics, Diabetes Center, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 107:10791-8. 2010
    ..Despite mounting evidence that the highly homologous insulin receptor (IR) can also convey protumorigenic signals, its direct role in cancer progression has not been genetically ..
  28. pmc Role for neuronal insulin resistance in neurodegenerative diseases
    Markus Schubert
    Institute for Genetics, University of Cologne, D 50931 Cologne, Germany
    Proc Natl Acad Sci U S A 101:3100-5. 2004
    ..contributes to defects in neuronal function, we have performed a detailed analysis of brain/neuron-specific insulin receptor knockout (NIRKO) mice...
  29. pmc Insulin signalling and insulin actions in the muscles and livers of insulin-resistant, insulin receptor substrate 1-deficient mice
    T Yamauchi
    Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan
    Mol Cell Biol 16:3074-84. 1996
    We and others recently generated mice with a targeted disruption of the insulin receptor substrate 1 (IRS-1) gene and demonstrated that they exhibited growth retardation and had resistance to the glucose-lowering effect of insulin...
  30. pmc The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth
    Tadahiro Kitamura
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
    J Clin Invest 110:1839-47. 2002
    ..Mice lacking insulin receptor substrate-2 (Irs2) develop beta cell failure, suggesting that insulin signaling is required to maintain an ..
  31. ncbi Insulin and the insulin receptor in experimental models of learning and memory
    Wei Qin Zhao
    Blanchette Rockefeller Neurosciences Institute, 3rd Floor, Academic and Research Building, 9601 Medical Center Drive, Rockville, MD 20850, USA
    Eur J Pharmacol 490:71-81. 2004
    ..In the central nervous system (CNS), insulin and the insulin receptor are found in specific brain regions where they show evidence of participation in a variety of region-specific ..
  32. ncbi The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307)
    V Aguirre
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 275:9047-54. 2000
    ..These results suggest that phosphorylation of serine 307 might mediate, at least partially, the inhibitory effect of proinflammatory cytokines like TNFalpha on IRS-1 function...
  33. ncbi Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity
    P Auberger
    Centre CNRS INSERM de Pharmacologie Endocrinologie, Montpellier, France
    Cell 58:631-40. 1989
    ..pp63 purified by affinity chromatography inhibited insulin receptor tyrosine kinase and receptor autophosphorylation. Only the phosphorylated form of the protein was active...
  34. ncbi Distinct and overlapping functions of insulin and IGF-I receptors
    J Nakae
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Endocr Rev 22:818-35. 2001
    ..IGF-I receptor mediates IGF-I and IGF-II action on prenatal growth and IGF-I action on postnatal growth. Insulin receptor mediates prenatal growth in response to IGF-II and postnatal metabolism in response to insulin...
  35. ncbi Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan
    Nataliya Libina
    Department of Biochemistry and Biophysics, Mission Bay Genentech Hall, 600 16th Street, Room S312D, University of California, San Francisco, San Francisco, CA 94143, USA
    Cell 115:489-502. 2003
    ..We suggest that this network of tissue interactions and feedback regulation allows the tissues to equilibrate and fine-tune their expression of downstream genes, which, in turn, coordinates their rates of aging within the animal...
  36. ncbi Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes
    A Ullrich
    Nature 313:756-61. 1985
    We have deduced the entire 1,370-amino-acid sequence of the human insulin receptor precursor from a single complementary DNA clone...
  37. ncbi Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B
    A Salmeen
    Laboratory of Molecular Biophysics, University of Oxford, South Parks Road, Oxford, OX1 3QU, United Kingdom
    Mol Cell 6:1401-12. 2000
    ..for negatively regulating insulin signaling by dephosphorylating the phosphotyrosine residues of the insulin receptor kinase (IRK) activation segment...
  38. pmc Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity
    A Ullrich
    EMBO J 5:2503-12. 1986
    ..In analogy with the 152,784 Mr insulin receptor precursor, cleavage of the Arg-Lys-Arg-Arg sequence at position 707 of the IGF-I receptor precursor will ..
  39. ncbi MBNL1 is the primary determinant of focus formation and aberrant insulin receptor splicing in DM1
    Warunee Dansithong
    Department of Biochemistry and Molecular Biology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
    J Biol Chem 280:5773-80. 2005
    ..DMPK RNA into RNA-protein complexes containing MBNL1 and MBNL2 has been linked to aberrant splicing of the insulin receptor (IR) RNA...
  40. pmc Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo
    Shu Ling Chiu
    Watson School of Biological Sciences and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Neuron 58:708-19. 2008
    b>Insulin receptor signaling has been postulated to play a role in synaptic plasticity; however, the function of the insulin receptor in CNS is not clear...
  41. ncbi Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein
    D J Clancy
    Department of Biology, University College London, Wolfson House, 4 Stephenson Way, London NW1 2HE, UK
    Science 292:104-6. 2001
    The Drosophila melanogaster gene chico encodes an insulin receptor substrate that functions in an insulin/insulin-like growth factor (IGF) signaling pathway...
  42. ncbi Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway
    R Y Lee
    Present addresses WormBase, Division of Biology, California Institute of Technology 156 29, Pasadena, CA 91125, USA
    Curr Biol 11:1950-7. 2001
    ..Together, these observations suggest that the combined effects of transcriptional and posttranslational regulation of daf-16 transduce insulin-like signals in C. elegans and perhaps more generally...
  43. pmc Molecular mechanism of insulin-induced degradation of insulin receptor substrate 1
    Rachel Zhande
    Endocrinology Division, University of Vermont College of Medicine, Burlington, Vermont 05405, USA
    Mol Cell Biol 22:1016-26. 2002
    b>Insulin receptor substrate 1 (IRS-1) plays an important role in the insulin signaling cascade...
  44. ncbi Cinnamon extract and polyphenols affect the expression of tristetraprolin, insulin receptor, and glucose transporter 4 in mouse 3T3-L1 adipocytes
    Heping Cao
    Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Beltsville, MD 20705 2350, USA
    Arch Biochem Biophys 459:214-22. 2007
    ..The objective of this study was to investigate the effects of cinnamon on the protein and mRNA levels of insulin receptor (IR), glucose transporter 4 (GLUT4), and tristetraprolin (TTP/ZFP36) in mouse 3T3-L1 adipocytes...
  45. ncbi Opposing activities protect against age-onset proteotoxicity
    Ehud Cohen
    Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 313:1604-10. 2006
    ..Because the IIS pathway is central to the regulation of longevity and youthfulness in worms, flies, and mammals, these results suggest a mechanistic link between the aging process and aggregation-mediated proteotoxicity...
  46. ncbi The role of insulin receptor signaling in synaptic plasticity and cognitive function
    Chiung Chun Huang
    Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
    Chang Gung Med J 33:115-25. 2010
    ..In recent years, various functions for insulin receptor signaling in the brain have been suggested in normal neurophysiology, and a dysregulation of insulin ..
  47. pmc Acute physical exercise reverses S-nitrosation of the insulin receptor, insulin receptor substrate 1 and protein kinase B/Akt in diet-induced obese Wistar rats
    Jose R Pauli
    Departamento de Clinica Medica, FCM UNICAMP, Universidade Estadual de Campinas, Campinas, SP, Brasil
    J Physiol 586:659-71. 2008
    ..We demonstrated that a high-fat diet led to an increase in the iNOS protein level and S-nitrosation of insulin receptor beta (IR beta), insulin receptor substrate 1 (IRS1) and Akt...
  48. ncbi Molecular mechanisms of differential intracellular signaling from the insulin receptor
    Maja Jensen
    Hagedorn Research Institute, 2820 Gentofte, Denmark
    Vitam Horm 80:51-75. 2009
    Binding of insulin to the insulin receptor (IR) leads to a cascade of intracellular signaling events, which regulate multiple biological processes such as glucose and lipid metabolism, gene expression, protein synthesis, and cell growth, ..
  49. ncbi Quantitative mass spectrometry identifies insulin signaling targets in C. elegans
    Meng Qiu Dong
    Scripps Research Institute, La Jolla, CA92037, USA
    Science 317:660-3. 2007
    DAF-2, an insulin receptor-like protein, regulates metabolism, development, and aging in Caenorhabditis elegans...
  50. ncbi Structural biology of insulin and IGF1 receptors: implications for drug design
    Pierre De Meyts
    Receptor Biology Laboratory, Hagedorn Research Institute, Niels Steensens Vej 6, DK 2820 Gentofte, Denmark
    Nat Rev Drug Discov 1:769-83. 2002
    ....
  51. ncbi Role of brain insulin receptor in control of body weight and reproduction
    J C Bruning
    Klinik II und Poliklinik für Innere Medizin and Center of Molecular Medicine ZMMK der Universität zu Köln, Joseph Stelzmann Strasse 9, 50931 Cologne, Germany
    Science 289:2122-5. 2000
    ..Thus, IR signaling in the CNS plays an important role in regulation of energy disposal, fuel metabolism, and reproduction...
  52. pmc Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth
    Krisztina Kisfalvi
    Departments of Medicine, CURE, Digestive Diseases Research Center, Molecular Biology Institute, University of California at Los Angeles, 90095 1786, USA
    Cancer Res 69:6539-45. 2009
    ..Here, we determined whether metformin disrupts the crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells...
  53. ncbi Serum alpha 2-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level
    P R Srinivas
    Center for Molecular Biology, Wayne State University, Detroit, Michigan 48201
    Mol Endocrinol 7:1445-55. 1993
    The insulin-dependent tyrosine kinase activity (TKA) of the insulin receptor (IR) plays an essential role in insulin signaling. Thus, dysregulation of IR-TKA might be an important element in the states of insulin resistance...
  54. pmc Divergent regulation of energy expenditure and hepatic glucose production by insulin receptor in agouti-related protein and POMC neurons
    Hua V Lin
    Department of Medicine, Columbia University, New York, New York, USA
    Diabetes 59:337-46. 2010
    ..We have shown that mice with hypothalamic deficiency (L1) of insulin receptors (InsRs) fail to regulate hepatic glucose production (HGP) in response to insulin...
  55. ncbi Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression
    Hao Zhang
    Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
    Metabolism 59:285-92. 2010
    Our previous work demonstrated that berberine (BBR) increases insulin receptor (InsR) expression and improves glucose utility both in vitro and in animal models...
  56. ncbi The insulin receptor: a prototype for dimeric, allosteric membrane receptors?
    Pierre De Meyts
    Receptor Systems Biology Laboratory, Hagedorn Research Institute, Niels Steensens Vej 6, Gentofte, Denmark
    Trends Biochem Sci 33:376-84. 2008
    The recent crystallographic structure of the insulin receptor (IR) extracellular domain has brought us closer to ending several decades of speculation regarding the stoichiometry and mechanism of insulin-receptor binding and negative ..
  57. ncbi Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1
    H Tamemoto
    Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan
    Nature 372:182-6. 1994
    b>Insulin receptor substrate-1 (IRS-1) is the major substrate of insulin receptor and IGF-1 receptor tyrosine kinases; it has an apparent relative molecular mass of 160-190,000 (M(r), 160-190K) on SDS polyacrylamide gel...
  58. ncbi Testis determination requires insulin receptor family function in mice
    Serge Nef
    Center for Developmental Biology, University of Texas, Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390 9133, USA
    Nature 426:291-5. 2003
    ..Here we show that the insulin receptor tyrosine kinase family, comprising Ir, Igf1r and Irr, is required for the appearance of male gonads and thus ..
  59. ncbi Regulation of insulin receptor function
    J F Youngren
    Mount Zion Medical Center, Diabetes and Endocrine Research, University of California at San Francisco, San Francisco, CA 94143 1616, USA
    Cell Mol Life Sci 64:873-91. 2007
    ..this decrement in insulin signaling begins with either the activation or substrate kinase activity of the insulin receptor (IR), which is the only component of the pathway that is unique to insulin action...
  60. ncbi Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells
    G Zeng
    Hypertension Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1755, USA
    Circulation 101:1539-45. 2000
    ..Previously, we demonstrated that insulin stimulates production of nitric oxide (NO) in endothelial cells. However, specific insulin-signaling pathways mediating production of NO have not been elucidated...
  61. ncbi Cholesterol depletion disrupts caveolae and insulin receptor signaling for metabolic control via insulin receptor substrate-1, but not for mitogen-activated protein kinase control
    S Parpal
    Department of Cell Biology, Faculty of Health Sciences, , , Sweden
    J Biol Chem 276:9670-8. 2001
    ..Insulin access to or affinity for the insulin receptor on rat adipocytes was not affected as determined by (125)I-insulin binding...
  62. ncbi The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans
    Y Honda
    Tokyo Metropolitan Institute of Gerontology, Tokyo 173 0015, Japan
    FASEB J 13:1385-93. 1999
    ..Mutations in the daf-2 gene, which encodes a member of the insulin receptor family, confer the life extension (Age) phenotype and the constitutive dauer (a growth-arrested larval form ..
  63. pmc Insulin receptor splicing alteration in myotonic dystrophy type 2
    R S Savkur
    Department of Pathology, Baylor University, Houston, TX, USA
    Am J Hum Genet 74:1309-13. 2004
    ..We now demonstrate that comparable splicing abnormalities occur in DM2 muscle prior to the development of muscle histopathology, thus demonstrating an early pathogenic effect of RNA expansions...
  64. pmc Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway
    Oscar Puig
    Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    Genes Dev 17:2006-20. 2003
    The Drosophila insulin receptor (dInR) regulates cell growth and proliferation through the dPI3K/dAkt pathway, which is conserved in metazoan organisms...
  65. ncbi Epigenetic malprogramming of the insulin receptor promoter due to developmental overfeeding
    Andreas Plagemann
    Division of Experimental Obstetrics, Clinic of Obstetrics, Charite University Medicine Berlin, Campus Virchow Klinikum, Berlin, Germany
    J Perinat Med 38:393-400. 2010
    ..g., due to induction of hypothalamic insulin resistance. We investigated acquired alterations of the DNA methylation pattern of the hypothalamic insulin receptor promoter (IRP) which might be an underlying molecular mechanism.
  66. pmc Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistance
    Terumasa Okada
    Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 104:8977-82. 2007
    ..In the first model, we used liver-specific insulin receptor knockout (LIRKO) mice, which exhibit hyperinsulinemia without developing diabetes due to a compensatory ..
  67. ncbi Glucose metabolism and insulin receptor signal transduction in Alzheimer disease
    Siegfried Hoyer
    Department of Pathology, University of Heidelberg, Im Neuenheimer Feld 220 221, 69120 Heidelberg, Germany
    Eur J Pharmacol 490:115-25. 2004
    ..In early-onset familial Alzheimer disease, the inhibition of neuronal insulin receptor function may be due to competitive binding of amyloid beta (Abeta) to the insulin receptor...
  68. ncbi Molecular mechanism of insulin resistance in type 2 diabetes mellitus: role of the insulin receptor variant forms
    G Sesti
    University of Catanzaro Magna, Graecia, Italy
    Diabetes Metab Res Rev 17:363-73. 2001
    ..Due to its pivotal role in insulin action, the insulin receptor was considered a plausible candidate gene...
  69. pmc Inhibition of cancer cell proliferation and metastasis by insulin receptor downregulation
    H Zhang
    Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
    Oncogene 29:2517-27. 2010
    b>Insulin receptor (IR) and the type I IGF receptor (IGF1R) are structurally and functionally related. The function of IGF1R in cancer has been well documented and anti-IGF1R strategies to treat cancer have shown initial positive results...
  70. pmc Human biliverdin reductase: a member of the insulin receptor substrate family with serine/threonine/tyrosine kinase activity
    Nicole Lerner-Marmarosh
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14624, USA
    Proc Natl Acad Sci U S A 102:7109-14. 2005
    ..BVR is both a substrate for insulin receptor (IR) tyrosine kinase (IRK) activity and a kinase for serine phosphorylation of IR substrate 1 (IRS-1)...
  71. ncbi Insulin receptor substrate and p55 orthologous adaptor proteins function in the Caenorhabditis elegans daf-2/insulin-like signaling pathway
    Catherine A Wolkow
    Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    J Biol Chem 277:49591-7. 2002
    ..elegans insulin pathway did not identify homologs of insulin receptor substrates or the phosphoinositide 3-kinase (PI3K) adaptor/regulatory subunit, which are both required for ..
  72. ncbi The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121)
    B V Costanzo
    Institute of Internal Medicine, Endocrine and Metabolic Diseases, University of Catania, Ospedale Garibaldi, Italy
    Diabetes 50:831-6. 2001
    ..the membrane glycoprotein PC-1 may play a role in human insulin resistance through the inhibition of insulin receptor (IR) autophosphorylation...
  73. pmc Embryonic morphogenesis in Caenorhabditis elegans integrates the activity of LET-502 Rho-binding kinase, MEL-11 myosin phosphatase, DAF-2 insulin receptor and FEM-2 PP2c phosphatase
    A J Piekny
    Genes and Development Research Group and Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada
    Genetics 156:1671-89. 2000
    ..In contrast mig-2 (Rho/Rac), daf-2 (insulin receptor), and age-1 (PI3 kinase) act within the let-502/mel-11 pathway...
  74. ncbi In vivo regulation of phosphoinositide 3-kinase in retina through light-induced tyrosine phosphorylation of the insulin receptor beta-subunit
    Raju V S Rajala
    Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
    J Biol Chem 277:43319-26. 2002
    ..rod outer segment (ROS) is activated in vitro by tyrosine phosphorylation of the C-terminal tail of the insulin receptor (Rajala, R. V. S., and Anderson, R. E. (2001) Invest. Ophthal. Vis. Sci. 42, 3110-3117)...
  75. pmc The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance
    David Vicent
    Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 111:1373-80. 2003
    ....
  76. ncbi HMGA1 controls transcription of insulin receptor to regulate cyclin D1 translation in pancreatic cancer cells
    Sebastian Kolb
    Department of Internal Medicine II, Technical University of Munich, Ismaninger, Munich, Germany
    Cancer Res 67:4679-86. 2007
    ..We show that 4E-BP1 and cyclin D1 act downstream of the insulin receptor (IR) in pancreatic cancer cells...
  77. ncbi Insulin receptor isoform A and insulin-like growth factor II as additional treatment targets in human osteosarcoma
    Sofia Avnet
    Laboratory for Pathophysiology, Rizzoli Orthopaedic Institute, Bologna, Italy
    Cancer Res 69:2443-52. 2009
    ..Also, isoform A of the insulin receptor (IR-A) was expressed at high level in addition to IGFIR and IR-A/IGFIR hybrids receptors (HR(A))...
  78. ncbi A homogenous assay to monitor the activity of the insulin receptor using Bioluminescence Resonance Energy Transfer
    Tarik Issad
    Department of Cell Biology, Cochin Institute, CNRS, INSERM, University Rene Descartes, 22 rue Mechain, 75014 Paris, France
    Biochem Pharmacol 64:813-7. 2002
    ..The discovery of pharmacological agents that specifically activate the tyrosine kinase activity of the insulin receptor will be of great importance for the treatment of insulin-resistant or insulin-deficient patients...
  79. ncbi Sam68 is a docking protein linking GAP and PI3K in insulin receptor signaling
    V Sanchez-Margalet
    Department of Medical Biochemistry and Molecular Biology, School of Medicine, University of Seville and Investigation Unit, University Hospital Virgen Macarena, Av Sanchez Pizjuan 4, 41009 Seville, Spain
    Mol Cell Endocrinol 183:113-21. 2001
    ..We have recently found that Sam68 is a substrate of the insulin receptor (IR) and that Tyr-phosphorylated Sam68 associates with the SH2 domains of p85 PI3K...
  80. ncbi Insulin-induced insulin receptor substrate-1 degradation is mediated by the proteasome degradation pathway
    X J Sun
    Endocrinology Division, University of Vermont College of Medicine, Burlington 05405, USA
    Diabetes 48:1359-64. 1999
    b>Insulin receptor substrate (IRS) proteins are important intracellular molecules that mediate insulin receptor tyrosine kinase signaling...
  81. pmc Contribution of impaired myocardial insulin signaling to mitochondrial dysfunction and oxidative stress in the heart
    Sihem Boudina
    University of Utah School of Medicine, Salt Lake City, 84112, USA
    Circulation 119:1272-83. 2009
    ..The present study tested the hypothesis that perinatal loss of insulin signaling in the heart impairs mitochondrial function...
  82. ncbi Insulin/IGF signalling in neurogenesis
    J M Bateman
    The Wolfson Centre for Age Related Disease, King s College London, Hodgkin Building, Guy s Campus, London, United Kingdom
    Cell Mol Life Sci 63:1701-5. 2006
  83. ncbi Chronic kidney disease causes defects in signaling through the insulin receptor substrate/phosphatidylinositol 3-kinase/Akt pathway: implications for muscle atrophy
    James L Bailey
    Renal Division, Emory University School of Medicine, WMB 338, 1639 Pierce Drive, Atlanta, GA 30322, USA
    J Am Soc Nephrol 17:1388-94. 2006
    ..Postreceptor signaling through the insulin receptor substrate (IRS)/PI3-K/Akt pathway was evaluated in muscles of acidotic, CKD and pair-fed control rats under ..
  84. pmc Interaction with Grb14 results in site-specific regulation of tyrosine phosphorylation of the insulin receptor
    Sebastien Nouaille
    Departement de Biologie Cellulaire, Institut Cochin, Universite Paris Descartes, 22 rue Mechain, UMRCNRS 8104, INSERM U567, Paris 75014, France
    EMBO Rep 7:512-8. 2006
    The dynamics of interaction of the insulin receptor (IR) with Grb14 was monitored, in real time, in living human embryonic kidney cells, using bioluminescence resonance energy transfer (BRET)...
  85. ncbi Selective response to insulin versus insulin-like growth factor-I and -II and up-regulation of insulin receptor splice variant B in the differentiated mouse mammary epithelium
    Chiara Berlato
    Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria
    Endocrinology 150:2924-33. 2009
    ..However, our analysis of the expression levels of IGF-IR and the two insulin receptor (IR) splice variants, IR-A and IR-B, has revealed a 3- to 4-fold up-regulation of IR-B transcripts and a 6-..
  86. ncbi The functional significance of Shc in insulin signaling as a substrate of the insulin receptor
    T Sasaoka
    Department of Clinical Pharmacology, Toyama Medical and Pharmaceutical University, Japan
    Endocr J 47:373-81. 2000
    ..Upon insulin stimulation, the activated insulin receptor interacts with Shc...
  87. ncbi Metformin rapidly increases insulin receptor activation in human liver and signals preferentially through insulin-receptor substrate-2
    Jenny E Gunton
    Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, Sydney, New South Wales 2065 Australia
    J Clin Endocrinol Metab 88:1323-32. 2003
    ..Huh7 human hepatoma cells and primary human hepatocytes were used. Insulin receptor (IR) and IR substrates (IRS)-1 and -2 were assessed by immunoprecipitation and immunoblot...
  88. ncbi A PDZ domain protein interacts with the C-terminal tail of the insulin-like growth factor-1 receptor but not with the insulin receptor
    T Ligensa
    Roche Diagnostics GmbH, Pharma Research, Nonnenwald 2, Penzberg 82372, Germany
    J Biol Chem 276:33419-27. 2001
    ..factor-1 (IGF-1) receptor-interacting protein-1, which binds to the IGF-1 receptor, but not to the related insulin receptor, and which is involved in the regulation of cell motility...
  89. ncbi Interaction of the insulin receptor with the receptor-like protein tyrosine phosphatases PTPalpha and PTPepsilon in living cells
    Daniele Lacasa
    Department of Cell Biology, Institut Cochin, CNRS UMR 8104, INSERM U567, Universite Paris V, 22 rue Mechain, 75014 Paris, France
    Mol Pharmacol 67:1206-13. 2005
    The interactions between the insulin receptor and the two highly homologous receptor-like protein tyrosine phosphatases (PTPase) PTPalpha and PTPepsilon were studied in living cells by using bioluminescence resonance energy transfer...
  90. ncbi Effects of the long-acting insulin analog insulin glargine on cultured human skeletal muscle cells: comparisons to insulin and IGF-I
    T P Ciaraldi
    Veterans Affairs San Diego HealthCare System 9111G and Department of Medicine, University of California San Diego, La Jolla, California 92093, USA
    J Clin Endocrinol Metab 86:5838-47. 2001
    ..We conclude that in human skeletal muscle cells, insulin glargine is equivalent to human insulin for metabolic responses and does not display augmented mitogenic effects...
  91. pmc Enhanced retinal insulin receptor-activated neuroprotective survival signal in mice lacking the protein-tyrosine phosphatase-1B gene
    Raju V S Rajala
    Department of Ophthalmology, Dean A McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
    J Biol Chem 285:8894-904. 2010
    ..We previously demonstrated that light-induced tyrosine phosphorylation of the retinal insulin receptor (IR) results in the activation of phosphoinositide 3-kinase/Akt survival pathway in rod photoreceptor cells...
  92. pmc Functionally distinct insulin receptors generated by tissue-specific alternative splicing
    L Mosthaf
    Department of Developmental Biology, Genentech, Inc, South San Francisco, CA 90480
    EMBO J 9:2409-13. 1990
    Cloning of the insulin receptor cDNA has earlier revealed the existence of two alternative forms of the receptor differing by the presence or absence of 12 amino acids near the C-terminus of the receptor alpha-subunit...
  93. ncbi Insulin-like signaling, nutrient homeostasis, and life span
    Akiko Taguchi
    Howard Hughes Medical Institute, Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, Karp Family Research Laboratories, Boston, MA 02115, USA
    Annu Rev Physiol 70:191-212. 2008
    ..We discuss the possibility that the brain is the site where reduced insulin-like signaling can consistently extend mammalian life span-just as reduced insulin-like signaling extends the life span of lower metazoans...
  94. ncbi Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
    J C Yoon
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 413:131-8. 2001
    ..These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver...
  95. pmc Muscleblind-like 1 (Mbnl1) promotes insulin receptor exon 11 inclusion via binding to a downstream evolutionarily conserved intronic enhancer
    Supriya Sen
    Medical Research Service, Veterans Affairs San Diego Healthcare System, San Diego, California, USA
    J Biol Chem 285:25426-37. 2010
    The insulin receptor exists as two isoforms, IR-A and IR-B, which result from alternative splicing of exon 11 in the primary transcript...
  96. pmc Expression of insulin receptor isoform A and insulin-like growth factor-1 receptor in human acute myelogenous leukemia: effect of the dual-receptor inhibitor BMS-536924 in vitro
    Andrea E Wahner Hendrickson
    Departments of Medicine and Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Cancer Res 69:7635-43. 2009
    The insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) are receptor tyrosine kinases that participate in mitogenic and antiapoptotic signaling in normal and neoplastic epithelia...
  97. ncbi Annexin II is a novel player in insulin signal transduction. Possible association between annexin II phosphorylation and insulin receptor internalization
    Y Biener
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 271:29489-96. 1996
    ..This was evident in CHO cells, overexpressing the insulin receptor, in which internalization was inhibited either by tyrosine kinase inhibitors or by lowering the temperature ..
  98. ncbi Protein tyrosine phosphatase 1B interacts with the activated insulin receptor
    B L Seely
    Department of Medicine, University of California, San Diego, La Jolla, USA
    Diabetes 45:1379-85. 1996
    ..We have investigated the interaction of PTP1B with the insulin receptor using a PTP1B glutathione S-transferase (GST) fusion protein with a point mutation in the enzyme's catalytic ..
  99. ncbi Insulin rescues retinal neurons from apoptosis by a phosphatidylinositol 3-kinase/Akt-mediated mechanism that reduces the activation of caspase-3
    A J Barber
    Department of Ophthalmology, Penn State Retina Research Group, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 276:32814-21. 2001
    ..The rescue effect of insulin does not appear to be mediated by NF-kappaB or p53. These data suggest that insulin provides trophic support for retinal neurons through a PI 3-kinase/Akt-dependent pathway...
  100. ncbi Plasma adiponectin as a marker of insulin receptor dysfunction: clinical utility in severe insulin resistance
    Robert K Semple
    Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
    Diabetes Care 31:977-9. 2008
    ..Identification of severely insulin-resistant patients who have genetic or acquired insulin receptor dysfunction may aid therapeutic decision making; however, onerous diagnostic tests allied to a low frequency ..
  101. pmc Preserved pancreatic beta-cell development and function in mice lacking the insulin receptor-related receptor
    T Kitamura
    Naomi Berrie Diabetes Center and Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Mol Cell Biol 21:5624-30. 2001
    ..The insulin receptor-related receptor (IRR) is an orphan receptor of the insulin receptor gene (Ir) subfamily...

Research Grants70

  1. Ang II and Aldosterone Effects on Insulin Resistance in Cardiovascular Tissue
    JAMES RUSSELL SOWERS; Fiscal Year: 2013
    ..insulin metabolic signaling by inducing site specific Ser phosphorylation of the critical docking protein insulin receptor substrate-1 (IRS-1)...
  2. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2011
    ..and growth factor signaling in the heart we generated mice with cardiomyocyte-restricted deletion of the insulin receptor substrates IRS-1 and IRS-2 (CIRS12KO)...
  3. INSULIN RECEPTORS AND THE GLUCOSE TRANSPORT SYSTEM
    JERROLD MICHAEL OLEFSKY; Fiscal Year: 2013
    ..These studies should lead to an improved understanding of the basic causes of Type 2 diabetes mellitus and hold the potential for new therapeutic modalities. ..
  4. Biology of IGFs in Bone
    Thomas L Clemens; Fiscal Year: 2013
    ..During the last funding period, we used mice lacking either IGF-1 or insulin receptor in osteoblasts to begin to distinguish actions of IGF-1 and insulin in the skeleton...
  5. Pathogenesis of the Metabolic Syndrome
    W Timothy Garvey; Fiscal Year: 2013
    ..serine kinases, such as PKC or IKK2 (in association with activation of NF-:B), which then phosphorylate insulin receptor substrate (IRS) molecules resulting in impaired insulin signal transduction...
  6. JNK exacerbates ischemia/reperfusion injury in hyperglycemic subjects.
    Keith A Webster; Fiscal Year: 2010
    ..a condition that sensitized myocytes to oxidative stress, and coincided with increased phosphorylation of the insulin receptor substrate-1 (IRS-1) on the inhibitory serine-307...
  7. PTEN TUMOR SUPPRESSOR AND SIGNAL TRANSDUCTION
    RAMON E PARSONS; Fiscal Year: 2012
    ..elegans and drosophila. In these species, PTEN acts downstream of the insulin/IGF receptor, the insulin receptor substrate (IRS) adaptor and PI-3 kinase and upstream of AKT kinase...
  8. A2b Adenosine Receptor Regulation of Metabolic Disease and Inflammation
    Anna Eisenstein; Fiscal Year: 2013
    ..One important mediator of insulin signaling, the insulin receptor substrate 2 (IRS-2), is reduced by the action of inflammatory cytokines...
  9. Atypical PKC Knockout Models: Effect on Glucose and Lipid Homeostasis
    Robert V Farese; Fiscal Year: 2013
    ..in muscle and adipose tissues is diminished;however, these mice unexpectedly have poor activation of the insulin receptor and Akt, as well as aPKC, in muscle, adipose and liver tissues...
  10. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2013
    ..yawning gap in our knowledge of insulin signaling, and has identified a cellular biological mechanism linking Insulin Receptor activation to regulation of the cell's transcriptional response through sub-cellular redistribution of ..
  11. Role of Membrane Modifications in the Bioactivities of Conjugated Linoleic Acids
    Papasani V Subbaiah; Fiscal Year: 2013
    ..The function of raft associated proteins, specifically those involved in the insulin receptor signaling pathway will be studied following the CLA enrichment and insulin stimulation of the cells in vitro...
  12. Mechanisms of Diabetic Hyperphagia and Insulin Resistance
    Michael W Schwartz; Fiscal Year: 2012
    ..At the cellular level, signaling via the insulin receptor substrate-phosphotidylinositol-3 kinase (IRS-PI3K) pathway plays a critical role in insulin action in ..
  13. Evaluating Novel Multi-kinase Peptide Inhibitors as a Treatment for Rheumatoid Ar
    DAVID MEN HWEI TSAI; Fiscal Year: 2013
    ..of epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR2), and insulin receptor (IR)...
  14. Simultaneous Insulin and Leptin Signaling in POMC Neurons Promotes Fertility and
    LATRICE DOREEN FAULKNER; Fiscal Year: 2013
    ..Collectively, these experiments will establish whether the absence of insulin and leptin signaling in POMC neurons elevates LH pulse secretion and testosterone release, thus impairing the steroidal negative feedback. ..
  15. Primate Fetal Adrenal Development: Impact on Physiological Processes After Birth
    Eugene D Albrecht; Fiscal Year: 2013
    ..and/or by restraining fetal adrenocortical zone androgen secretion, developmentally program components of the insulin receptor signaling pathway within insulin target tissues, i.e...
  16. Tunable Insulin Resistance in a Drosophila Model of Diabetes
    ELENA M GRACHEVA; Fiscal Year: 2010
    ..e. insulin receptor, or Chico, etc) and optimize this system so that flies die during pupal development...
  17. Selective Insulin Resistance- Diabetic Cardiovascular Diseases
    George L King; Fiscal Year: 2013
    ....
  18. MOUSE MODELS OF INSULIN RESISTANCE
    Domenico Accili; Fiscal Year: 2013
    ..We documented the contribution of Insulin Receptor, its main substrates and signaling intermediates to the key abnormalities of insulin resistance: decreased ..
  19. Exploring the Impact of Negative Energy Balance in Men with Prostate Cancer
    Wendy Demark-Wahnefried; Fiscal Year: 2013
    ..energy-related factors;b) rates of tumor proliferation and apoptosis;c) tumor immunohistochemical markers of insulin receptor, VEGF, AKT, and NFkB;and d) functional and health-related outcomes, i.e...
  20. Mechanisms of Lipid-Induced Hepatic Insulin Resistance
    Gerald I Shulman; Fiscal Year: 2013
    ..intracellular DAG activates protein kinase C5 (PKC5), directly leading to inhibition of insulin- stimulated insulin receptor kinase (IRK) activity...
  21. Diet, Insulin, Dopamine, and Reward.
    Margaret E Rice; Fiscal Year: 2013
    ..studies to in vivo behavior, experiments in Aim 3 will determine the effect of intrastriatal insulin and insulin receptor (InsR) antagonist injections on behavioral responses to rewarding brain stimulation and food- and drug-paired ..
  22. Trauma and Hemorrhage-Induced Skeletal Muscle Insulin Resistance
    JOSEPH LOUIS MESSINA; Fiscal Year: 2013
    ..tissue or tissues need to be targeted? Our recently published and preliminary data indicate that there are insulin receptor and post-receptor defects in insulin signaling that develop in skeletal muscle following surgical trauma and ..
  23. INSULIN RECEPTOR STRUCTURE AND TURNOVER
    C Ronald Kahn; Fiscal Year: 2013
    ..Since its inception, the grant has been focused on the insulin receptor, and to a lesser extent IGF-1 receptor, and their signaling capabilities and their alterations in physiologic ..
  24. Role of the Sex Hormones and Insulin/IGF-Axes in Endometrial Cancer Recurrence
    Howard D Strickler; Fiscal Year: 2012
    ..globulin (SHBG);(ii) tumor expression of IGF-I, IGF-II, IGFBP-1 and -3 mRNA (based on RT-PCR), and of the insulin receptor, IGF-I receptor, estrogen receptor, progesterone receptor (based on immuno-histochemistry)...
  25. Genome-wide Association Study: Fetal Hemoglobin Phenotypes in Sickle Cell Disease
    Betty Pace; Fiscal Year: 2009
    ..unreadable]-oxidation, and mitochondrial biogenesis inclusive of PGC-1[unreadable], GLUT4, hexokinase, citrate synthase, beta-hydroxyacyl CoA dehydrogenase, and the serine phosphorylation of insulin receptor substrate-1.
  26. Insulin as a Regulator of Microvascular Exchange
    Virginia H Huxley; Fiscal Year: 2013
    ..integration, cultured microvessel EC of males and females, respectively, will be used to determine which EC insulin receptor-mediated signaling mechanisms are sex-specific...
  27. Alternative Splicing of the Insulin Receptor Gene
    NICHOLAS J WEBSTER; Fiscal Year: 2013
    ..There are two variants of the insulin receptor (IR), which differ in the presence of 12-amino acids in the hormone-binding domain...
  28. Regulation of IGF-1 and Insulin Signaling by O-GlcNAc Glycosylation
    LAUREN ELIZABETH BALL; Fiscal Year: 2013
    ..The specificity of the pleiotropic effects elicited by IGF-1R activation are mediated by the insulin receptor substrates, IRS-1 and IRS-2, which are critical to the formation of new bone and maintaining coupling between ..
  29. Role of Insulin Receptors in the Kidney
    CAROLYN MARY ECELBARGER; Fiscal Year: 2013
    ..To better elucidate the role of the insulin receptor in the kidney, we have developed an transgenic mouse with "knockout" (KO) or deletion of the insulin receptor ..
  30. Adiponectin regulates nutrient transport in the placenta
    Theresa L Powell; Fiscal Year: 2009
    ..placental System A mediated amino acid transport by decreasing tyrosine phosphorylation of the insulin receptor (IR) and insulin-receptor substrate 1 (IRS-1)...
  31. Adiporedoxin, a Novel Player in Adipokine Secretion
    Paul F Pilch; Fiscal Year: 2013
    ..expression of adiporedoxin in cultured mouse adipocytes causes corresponding changes in the amount of the insulin receptor. What these three proteins have in common, aside for important physiological functions, is the need for ..
  32. Role of microRNAs in lipid metabolism and cardiovascular disease
    Carlos Fernandez Hernando; Fiscal Year: 2013
    ..hydroxyacyl-CoA- dehydrogenase (HADHB), key enzymes involved in the regulation of fatty acid oxidation, and insulin receptor substrate 2 (IRS2), which regulates insulin signaling...
  33. Steroid regulation of glucose utilization during early pregnancy.
    ANTONINA I FROLOVA; Fiscal Year: 2010
    ..to estradiol leads to hyperphosphorylation of c-Jun NH2-terminal kinase (JNK), leading to inactivation of the insulin receptor substrate-1 (IRS1) and development of insulin resistance...
  34. Pioglitazone & Exercise Effects on Older Aldults with MCI and Metabolic Syndrome
    Robert S Schwartz; Fiscal Year: 2010
    ..This study will assess novel metabolic treatments for patients with both MCI and MS, with the aim of delaying the progression of these patients to dementia. ..
  35. The Insulin/IGF-I Axis in Diabetic Osteopathy
    John L Fowlkes; Fiscal Year: 2013
    ..We also will study mice generated in our laboratory with conditional knock-out of the insulin receptor (IR) in osteoblasts (OIRKO mice) in regards to in utero skeletal development, postnatal affects on skeletal ..
  36. Nuclear IRS-1-DNA repair and mutagenesis in medulloblastoma
    Krzysztof Reiss; Fiscal Year: 2012
    ..The results from previous founding period demonstrate that Insulin Receptor Substrate 1 (IRS-1), which is the major cytosolic component of the IGF-I receptor signaling system, can ..
  37. Effects of Ethanol on Insulin Signaling in the Brain
    Suzanne M de la Monte; Fiscal Year: 2013
    ..Ethanol inhibition of insulin signaling is mediated at the insulin receptor (IR), and caused by impaired binding and attendant reductions in the transmission of survival signals...
  38. Hippocampal plasticity in co-morbid diabetes and depression
    LAWRENCE P contact REAGAN; Fiscal Year: 2010
    ..these mechanistic mediators is that diabetic animals exhibit a complex physiology that includes deficits in insulin receptor (IR) signaling, hyperglycemia and neuroendocrine dysfunction...
  39. Vascular Phenotypic Regulation by Growth Factors, Insulin and Glucose
    Lakshman Segar; Fiscal Year: 2011
    ..objective is to investigate how platelet-derived growth factor (PDGF) regulates glucose transport and insulin receptor signaling to influence phenotypic changes in vascular smooth muscle cells (VSMCs)...
  40. Raf Kinase Inhibitory Protein (RKIP): A New Hepatocellular Carcinoma Tumor Suppre
    John M Sedivy; Fiscal Year: 2010
    ..transgenic with liver-specific expression of the hepatitis virus Bx transcriptional regulator (HBx) and insulin receptor substrate-1 (IRS-1). HBx/IRS-1 animals develop hepatocellular dysplasia that progresses to HCC...
  41. HGF/HGFR Axis and Fatty Liver Disease
    Reza Zarnegar; Fiscal Year: 2013
    ..Our new preliminary data indicate that, in hepatocytes, the insulin receptor (IR) tyrosine kinase crosstalks with the Hepatocyte Growth Factor Receptor (HGFR) tyrosine kinase (also known ..
  42. Cytosolic O-Glycosylation and Insulin Signaling
    Gerald Warren Hart; Fiscal Year: 2013
    ..in insulin signaling and insulin resistance at many points in the insulin signaling pathway, particularly on insulin receptor substrate proteins (IRS)...
  43. ENaC Transport in Insulin Resistance: Role of Insulin &IGF-1 Receptors
    Vivek Bhalla; Fiscal Year: 2013
    ..Experimental studies have yielded conflicting results on the role of the insulin receptor in mediating renal sodium reabsorption...
  44. Insulin and IGF-1 regulation of the GnR H neuron
    Sara A DiVall; Fiscal Year: 2012
    ..IGF-1 receptor shares signaling pathways with the insulin receptor, increases GnRH expression in vitro, and in vivo plays a permissive role in puberty onset...
  45. Insulin Receptor Substrates and Insulin Action
    C Ronald Kahn; Fiscal Year: 2013
    ..Since its inception, a major focus of this grant has been the study of the role of phosphorylation of insulin receptor substrates (IRS) and their downstream partners in insulin action and insulin resistance...
  46. Insulin Sensitivity using Aerobic Interval Conditioning (ISAIC)
    Conrad P Earnest; Fiscal Year: 2010
    ..unreadable]-oxidation, and mitochondrial biogenesis inclusive of PGC-1[unreadable], GLUT4, hexokinase, citrate synthase, beta-hydroxyacyl CoA dehydrogenase, and the serine phosphorylation of insulin receptor substrate-1.
  47. MODULATION OF OLFACTORY BULB NEURON CURRENT PROPERTIES
    Debra Ann Fadool; Fiscal Year: 2013
    ..Interactions with signaling proteins in the insulin receptor kinase/phosphatase cascade regulate Kv1.3 ion channel activity. 2. Voltage-gated activity from Kv1...
  48. Targeting crosstalk between insulin and Gq signaling systems in pancreatic cancer
    JUAN ENRIQUE ROZENGURT; Fiscal Year: 2010
    ..Crosstalk between the insulin receptor and G protein-coupled receptor (GPCR) signaling systems plays a critical role in the regulation of many ..
  49. Prospective evaluation of IGF and IL-6 Dysregulation and Multiple Myeloma
    Graham A Colditz; Fiscal Year: 2010
    ..Specific polymorphisms and haplotypes in the IGF-I, IGFBP-1,-2, and -3, IGF-I receptor (IGF-IR), and insulin receptor substrate (IRS)-1 and -2 genes are associated with increased risk of MM 2...
  50. siRNA-gold nanoparticle mediated ganglioside depletion for diabetic wound healing
    AMY SUSAN PALLER; Fiscal Year: 2013
    ..We will then examine the effect of gangliosides on insulin receptor (IR), insulin-like growth factor-1 receptor-integrin (IGF- 1R), and epidermal growth factor receptor (EGFR) ..
  51. Early Life Nutritional Environments and Cognitive Ability in Children
    Rika Tanda; Fiscal Year: 2012
    ..The results of this research may provide insight in developing public health strategies for preventing untoward consequence of childhood obesity epidemic. ..
  52. Bioactives in Blueberries and Insulin Resistance
    APRIL STULL; Fiscal Year: 2013
    ..e., Insulin receptor (IR), insulin receptor substrate (IRS), phosphatidylinositol-3 kinase (PI-3K), and Akt)) and -independent (i...
  53. Decreased CNS leptin activity in co-morbid depression and obesity
    Lawrence P Reagan; Fiscal Year: 2013
    ..blocks BBB transport of leptin and using a lentivirus vector that selectively downregulates hypothalamic insulin receptor expression (hypo-IRAS)...
  54. Insulin Action on GLUT4 and FOXO1 in the Brain
    Garrett Heinrich; Fiscal Year: 2012
    ..loss- or gain-of-function of hypothalamic insulin action mouse models will be generated by deleting the insulin receptor or Foxo1, respectively, in cells that express Nkx2.1...
  55. Hypothalamic glucokinase in obesity and diabetes
    Charles V Mobbs; Fiscal Year: 2010
    ..Interestingly, homozygous whole-body ablation of the insulin receptor also produces lethal neonatal diabetes, and neuron-specific expression of the insulin receptor partially ..
  56. Potassium Channel Dysfunction in Cerebral Arteries
    David W Busija; Fiscal Year: 2013
    ..Current treatment regimens are not optimal and we expect that the results of our studies will lead to new and improved therapies to prevent or slow the onset of neurological diseases in an obese and aging population. ..
  57. Adipose Tissue Amyloid Precursor Protein and Beta-Amyloid
    William G Tharp; Fiscal Year: 2013
    ..Specific Aim 3: To determine whether Ab affects glucose uptake in adipose tissue cells through alterations of insulin receptor signaling and pro-inflammatory pathways...
  58. FUNCTIONS AND INTERACTIONS DFOXO IN DROSOPHILA AGING
    Marc Tatar; Fiscal Year: 2013
    ..Activated insulin receptor represses the transcription factor FOXO...
  59. Regulation of Retinal Cell Death in Diabetes
    Thomas W Gardner; Fiscal Year: 2013
    ..The investigators have demonstrated that retinal pro-survival signaling via the insulin receptor and Akt is normally activated by insulin, insulin-like growth factors and light, and diabetes reduces this ..
  60. Regulating IRS1 by Ser/Thr Phosphorylation
    Morris F White; Fiscal Year: 2013
    ..responsiveness to insulin in muscle, liver and other tissues, including the CNS, depends upon the insulin receptor substrate proteins, IRS1 and IRS2...
  61. Analysis of Protein Dynamics in C. elegans by mLC/MS/MS
    Michael MacCoss; Fiscal Year: 2013
    ..elegans in response to the inhibition and overexpression of ligands of the insulin receptor (DAF-2)...
  62. Drug Delivery to CNS Endothelial Cells by Targeting Peptide-MHC Complexes
    Ulrich Bickel; Fiscal Year: 2009
    ..g. transferrin or insulin receptor) are not truly brain specific...
  63. REGULATION OF PLASMA CELL MALIGNANCY BY INSULIN AND IGF
    GREGORY FREUND; Fiscal Year: 2000
    ..Cellular responses included, phosphorylation of insulin receptor substrate-1 (IRS-1), activation of phosphatidylinositol 3- kinase (PI3-kinase), increased DNA synthesis and ..
  64. INSULIN AND PROSTACYCLIN IN ISCHEMIC HEART DISEASE
    ASRU SINHA; Fiscal Year: 1990
    ....
  65. ARF PROTEINS IN CELLULAR REGULATION OF PHOSPHOLIPASE D
    Guillermo Romero; Fiscal Year: 2000
    ..investigation of the possible mechanisms by which insulin might induce ARF activation revealed that the insulin receptor and ARF co-precipitate with immobilized insulin-agarose or with specific anti-insulin receptor antibodies...
  66. MOLECULAR COMPONENTS OF INSULIN RECEPTOR BIOGENESIS
    Joseph Bass; Fiscal Year: 2003
    ..Insulin resistance is a predisposing factor for diabetes and can be induced by impaired biogenesis of the insulin receptor, a transmembrane protein tyrosine kinase...
  67. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin U Devaskar; Fiscal Year: 2010
    ..at enhancing energy intake and conserving its expenditure consists of an increase in the hypothalamic insulin receptor, leptin receptor expression with an increase in neuropeptide Y, agouti-related peptide expression, and a ..
  68. INSULIN ACTION IN THE LIVER
    John Amatruda; Fiscal Year: 1992
    ..The role of the insulin receptor in phosphorylation of apo B will also be evaluated...
  69. SUBSTRATES FOR THE INSULIN RECEPTOR TYROSINE KINASE
    David Lebwohl; Fiscal Year: 1991
    The goal of this proposal is to identify and characterize endogenous substrates of the insulin receptor tyrosine protein kinase. The beta subunit of the insulin receptor is a tyrosine kinase...
  70. SURGERY OF THE PANCREAS--EFFECTS ON GLUCOSE METABOLISM
    Dana Andersen; Fiscal Year: 1999
    ..Recent animal and clinical studies of chronic pancreatitis-induced diabetes suggest that hepatic insulin receptor function and hepatic glucose transporter content are altered in this disease...