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 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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

Research Grants

  1. Testosterone stimulation of insulin signalingin adipocytes
    Wayne E Taylor; Fiscal Year: 2010
  2. Testosterone stimulation of insulin signalingin adipocytes
    Wayne Taylor; Fiscal Year: 2009
  3. PATHOGENESIS, IMMUNODIAGNOSIS AND THERAPY OF HCC
    Jack Wands; Fiscal Year: 2007
  4. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2003
  5. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2004
  6. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2002
  7. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2005
  8. Role of Insulin Receptors in the Kidney
    CAROLYN MARY ECELBARGER; Fiscal Year: 2010
  9. Role of Insulin Receptors in the Kidney
    CAROLYN MARY ECELBARGER; Fiscal Year: 2011
  10. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2010

Detail Information

Publications334 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 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...
  5. 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...
  6. 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...
  7. 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...
  8. 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)...
  9. 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...
  10. 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 ..
  11. 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 ..
  12. 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
  13. 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...
  14. 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...
  15. 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...
  16. 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...
  17. 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...
  18. doi 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...
  19. 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
    ....
  20. 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 ..
  21. doi 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...
  22. 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...
  23. 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...
  24. 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
    ....
  25. 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 ..
  26. 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 ..
  27. 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 ..
  28. 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...
  29. 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 ..
  30. 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...
  31. 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...
  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 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...
  34. 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...
  35. 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...
  36. 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...
  37. 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...
  38. 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 ..
  39. 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, ..
  40. 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...
  41. 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 ..
  42. doi 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...
  43. 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...
  44. 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...
  45. 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 ..
  46. 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...
  47. 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...
  48. 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...
  49. 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...
  50. 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)...
  51. 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 ..
  52. 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 ..
  53. 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...
  54. 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...
  55. 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...
  56. 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...
  57. doi 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-..
  58. 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)...
  59. 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...
  60. 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...
  61. 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...
  62. 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...
  63. 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...
  64. 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.
  65. 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...
  66. 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...
  67. 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...
  68. pmc Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2
    Y Kido
    Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20842, USA
    J Clin Invest 105:199-205. 2000
    ..signaling pathway in these processes, we have generated mice with combined heterozygous null mutations in insulin receptor (ir), insulin receptor substrate (irs-1), and/or irs-2...
  69. ncbi Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells
    Monica Montagnani
    Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1755, USA
    Mol Endocrinol 16:1931-42. 2002
    ..In this study, we evaluated roles of insulin receptor substrate 1 (IRS-1) and phosphoinositide-dependent kinase 1 (PDK-1) in production of NO...
  70. ncbi Reduced beta-cell mass and altered glucose sensing impair insulin-secretory function in betaIRKO mice
    Kenichi Otani
    Department of Medicine, Washington University School of Medicine, 660 S Euclid Avenue, Campus Box 8066, St Louis, MO 63110, USA
    Am J Physiol Endocrinol Metab 286:E41-9. 2004
    Pancreatic beta-cell-restricted knockout of the insulin receptor results in hyperglycemia due to impaired insulin secretion, suggesting that this cell is an important target of insulin action...
  71. ncbi The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's sarcoma
    P P Rose
    Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, OR, USA
    Oncogene 26:1995-2005. 2007
    ..The expression of the insulin receptor (IR) was strongly induced in latently infected E-DMVEC, whereas the expression levels of the IGF-IR remained ..
  72. ncbi Regulation of vascular endothelial growth factor expression and vascularization in the myocardium by insulin receptor and PI3K/Akt pathways in insulin resistance and ischemia
    Zhiheng He
    Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
    Arterioscler Thromb Vasc Biol 26:787-93. 2006
    ..This study characterized the role of insulin receptors and resistance on vascular endothelial growth factor (VEGF) expression and myocardial vascularization in physiological conditions and after ischemia...
  73. ncbi Critical nodes in signalling pathways: insights into insulin action
    Cullen M Taniguchi
    Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA
    Nat Rev Mol Cell Biol 7:85-96. 2006
    ..Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role using insulin signalling as a model system...
  74. ncbi Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and life span
    J Apfeld
    Department of Biochemistry and Biophysics, University of California, San Francisco 94143 0448, USA
    Cell 95:199-210. 1998
    ....
  75. ncbi The Drosophila insulin receptor is required for normal growth
    C Chen
    Department of Anatomy and Cell Biology, State University of New York, Brooklyn, New York 11203, USA
    Endocrinology 137:846-56. 1996
    Drosophila contain an insulin receptor homologue, encoded by the inr gene located at position 93E4-5 on the third chromosome...
  76. pmc Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1
    H Abe
    Second Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
    J Clin Invest 101:1784-8. 1998
    ..Thus, insulin resistance plays an important role in the clustering of coronary risk factors which may accelerate the progression of atherosclerosis in subjects with insulin resistance...
  77. ncbi Muscle insulin receptor concentrations in obese patients post bariatric surgery: relationship to hyperinsulinemia
    C Pender
    Department of Medicine, Division of Diabetes and Endocrine Research, Mount Zion Medical Center, University of California, San Francisco, San Francisco, CA, USA
    Int J Obes Relat Metab Disord 28:363-9. 2004
    ..Obesity results in insulin resistance. Bariatric surgery for obese individuals induces weight loss, improves insulin sensitivity, and lowers insulin levels. We investigated the mechanisms of this improvement...
  78. pmc SRp20 and CUG-BP1 modulate insulin receptor exon 11 alternative splicing
    Supriya Sen
    VA San Diego Healthcare System, San Diego, California 92161, USA
    Mol Cell Biol 29:871-80. 2009
    The insulin receptor (IR) exists as two isoforms, IR-A and IR-B, which result from alternative splicing of exon 11 in the primary transcript...
  79. ncbi Increased insulin sensitivity and upregulation of insulin receptor, insulin receptor substrate (IRS)-1 and IRS-2 in liver of Ames dwarf mice
    F P Dominici
    Instituto de Quimica y Fisicoquimica Biologicas, Facultad de Farmacia y Bioquimica, Junin 956, 1113, Buenos Aires, Argentina
    J Endocrinol 173:81-94. 2002
    ..The insulin-stimulated phosphorylation of the insulin receptor (IR) tended to be increased in the liver of Ames dwarf mice, while IR receptor protein content was increased ..
  80. ncbi Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body
    Dae Sung Hwangbo
    Division of Biology and Medicine, Box G W, Brown University, Providence, Rhode Island 02912, USA
    Nature 429:562-6. 2004
    ..These findings suggest that autonomous and non-autonomous roles of insulin signalling combine to control ageing...
  81. ncbi Reduced activation of phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes
    Karim Bouzakri
    INSERM U449 and CRNHL, IFR 62, R Laennec Medical Faculty, F 69370 Lyon Cedex 08, France
    Diabetes 52:1319-25. 2003
    ..stimulation of phosphatidylinositol (PI) 3-kinase activity, decreased association of PI 3-kinase with insulin receptor substrate (IRS)-1 and reduced IRS-1 tyrosine phosphorylation during insulin stimulation...
  82. pmc Structural resolution of a tandem hormone-binding element in the insulin receptor and its implications for design of peptide agonists
    Brian J Smith
    The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia
    Proc Natl Acad Sci U S A 107:6771-6. 2010
    The C-terminal segment of the human insulin receptor alpha-chain (designated alphaCT) is critical to insulin binding as has been previously demonstrated by alanine scanning mutagenesis and photo-cross-linking...
  83. ncbi The Gly-->Arg972 amino acid polymorphism in insulin receptor substrate-1 affects glucose metabolism in skeletal muscle cells
    M L Hribal
    Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy
    J Clin Endocrinol Metab 85:2004-13. 2000
    Molecular scanning of insulin receptor substrate-1 (IRS-1) revealed several amino acid substitutions. The most common IRS-1 variant, a Gly to Arg972 change, is more prevalent among type 2 diabetic patients...
  84. ncbi The OLD-1 positive regulator of longevity and stress resistance is under DAF-16 regulation in Caenorhabditis elegans
    S Murakami
    Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA
    Curr Biol 11:1517-23. 2001
    ..This study reveals a new system for specifying longevity and stress resistance and suggests possible mechanisms for mediating life extension by dietary restriction and hormesis...
  85. pmc Opposed growth factor signals control protein degradation in muscles of Caenorhabditis elegans
    Nathaniel J Szewczyk
    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
    EMBO J 26:935-43. 2007
    ....
  86. ncbi The insulin receptor isoform exon 11- (IR-A) in cancer and other diseases: a review
    A Denley
    School of Molecular and Biomedical Sciences, The University of Adelaide, Adelaide 5005, South Australia
    Horm Metab Res 35:778-85. 2003
    The insulin receptor plays a vital role in mediating the actions of insulin. These include metabolic and mitogenic effects...
  87. ncbi How insulin receptor substrate proteins regulate the metabolic capacity of the liver--implications for health and disease
    Louise Fritsche
    Department of Internal Medicine 4, Division of Clinical Chemistry and Pathobiochemistry, Central Laboratory, University Hospital Tuebingen, Tuebingen, Germany
    Curr Med Chem 15:1316-29. 2008
    ..Special attention will be paid to the insulin receptor substrate (IRS) proteins with the two major isoforms IRS-1 and IRS-2 as a critical node in hepatic insulin ..
  88. ncbi Soluble Abeta inhibits specific signal transduction cascades common to the insulin receptor pathway
    Matthew Townsend
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 282:33305-12. 2007
    ..An antagonist of the insulin receptor family of tyrosine kinases was found to mimic the pattern of Abeta-mediated kinase inhibition...
  89. pmc Glucose effects on beta-cell growth and survival require activation of insulin receptors and insulin receptor substrate 2
    Anke Assmann
    Joslin Diabetes Center, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02215, USA
    Mol Cell Biol 29:3219-28. 2009
    ..of exogenous glucose or insulin in beta-cell lines completely lacking either insulin receptors (betaIRKO) or insulin receptor substrate 2 (betaIRS2KO)...
  90. ncbi S-nitrosation of the insulin receptor, insulin receptor substrate 1, and protein kinase B/Akt: a novel mechanism of insulin resistance
    Marco A Carvalho-Filho
    Department of Internal Medicine, State University of Campinas, UNICAMP, Campinas, Brazil
    Diabetes 54:959-67. 2005
    ..Exogenous NO donated by S-nitrosoglutathione (GSNO) induced in vitro and in vivo S-nitrosation of the insulin receptor beta subunit (IRbeta) and protein kinase B/Akt (Akt) and reduced their kinase activity in muscle...
  91. ncbi Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats
    Christine Y Christ
    Department of Physiology, University of Texas Health Sciences Center, San Antonio, Texas 78712, USA
    J Appl Physiol 92:736-44. 2002
    ..whether the improvement in insulin action in response to exercise training is associated with enhanced insulin receptor signaling...
  92. 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...
  93. 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 ..
  94. ncbi The insulin receptor catalyzes the tyrosine phosphorylation of caveolin-1
    Akiko Kimura
    Department of Medicine, Life Sciences Institute, University of Michigan School of Medicine, Ann Arbor, Michigan 48109 0650, USA
    J Biol Chem 277:30153-8. 2002
    ..To explore the mechanisms involved in this event, we evaluated the association of the insulin receptor with caveolin...
  95. doi Importance of the solvent-exposed residues of the insulin B chain alpha-helix for receptor binding
    Tine Glendorf
    Diabetes Protein Engineering, Novo Nordisk A S, Novo Nordisk Park, DK 2760 Måløv, Denmark
    Biochemistry 47:4743-51. 2008
    ..of the B chain form a well-defined ridge, which is flanked and partly overlapped by the two described insulin receptor binding surfaces on either side of the insulin molecule...
  96. pmc Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric a{beta}
    Wei Qin Zhao
    Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
    J Biol Chem 284:18742-53. 2009
    ..In contrast, transfection of malfunctioning human insulin receptor mutants, identified originally from patient with insulin resistance syndrome, or inhibition of insulin and ..
  97. ncbi Hybrid receptors formed by insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant
    Rita Slaaby
    Novo Nordisk A S, Novo Alle, DK 2880 Bagsvaerd, Denmark
    J Biol Chem 281:25869-74. 2006
    b>Insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) are both from the same subgroup of receptor tyrosine kinases that exist as covalently bound receptor dimers at the cell surface...
  98. pmc Differential roles of insulin receptor substrates in brown adipocyte differentiation
    Yu Hua Tseng
    Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Cell Biol 24:1918-29. 2004
    Insulin promotes adipocyte differentiation via a complex signaling network involving multiple insulin receptor substrates (IRSs)...
  99. ncbi Role of insulin receptors and IGF receptors in growth and development
    K I Rother
    Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Pediatr Nephrol 14:558-61. 2000
    ..The clinical presentation regarding severity of growth retardation and metabolic disturbances observed in animal models versus in humans may differ greatly and the reasons will be reviewed in detail...
  100. ncbi IGF and insulin receptor signaling in breast cancer
    Antonino Belfiore
    Endocrinology, Department of Clinical and Experimental Medicine, University of Catanzaro, 88100, Catanzaro, Italy
    J Mammary Gland Biol Neoplasia 13:381-406. 2008
    ..One of these mechanisms is the aberrant expression of insulin receptor (IR) isoform A (IR-A), which is a high affinity receptor for both insulin and IGF-II, in breast cancer cells...
  101. 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...

Research Grants88

  1. Testosterone stimulation of insulin signalingin adipocytes
    Wayne E Taylor; Fiscal Year: 2010
    ..and myocytes or muscle cells by a multiple-step pathway involving the hormone insulin binding to the insulin receptor on the cell membrane and subsequent activation by phosphorylation of signaling molecules IRS-1 (insulin ..
  2. Testosterone stimulation of insulin signalingin adipocytes
    Wayne Taylor; Fiscal Year: 2009
    ..and myocytes or muscle cells by a multiple-step pathway involving the hormone insulin binding to the insulin receptor on the cell membrane and subsequent activation by phosphorylation of signaling molecules IRS-1 (insulin ..
  3. PATHOGENESIS, IMMUNODIAGNOSIS AND THERAPY OF HCC
    Jack Wands; Fiscal Year: 2007
    ..unreadable] During the last four years, we have made several significant observations: 1) the insulin receptor substrate-1 (IRS-1)[unreadable] signal transduction cascade plays a major role in hepatocyte proliferation...
  4. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2003
    ..Among the signaling cascades activated by insulin, the insulin receptor (IR), insulin receptor substrates (IRSs), phosphatidylinositol-3-phosphate kinase (PI 3-K) and Akt/PKB are ..
  5. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2004
    ..Among the signaling cascades activated by insulin, the insulin receptor (IR), insulin receptor substrates (IRSs), phosphatidylinositol-3-phosphate kinase (PI 3-K) and Akt/PKB are ..
  6. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2002
    ..Among the signaling cascades activated by insulin, the insulin receptor (IR), insulin receptor substrates (IRSs), phosphatidylinositol-3-phosphate kinase (PI 3-K) and Akt/PKB are ..
  7. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2005
    ..Among the signaling cascades activated by insulin, the insulin receptor (IR), insulin receptor substrates (IRSs), phosphatidylinositol-3-phosphate kinase (PI 3-K) and Akt/PKB are ..
  8. Role of Insulin Receptors in the Kidney
    CAROLYN MARY ECELBARGER; Fiscal Year: 2010
    ..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 ..
  9. Role of Insulin Receptors in the Kidney
    CAROLYN MARY ECELBARGER; Fiscal Year: 2011
    ..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 ..
  10. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2010
    ..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)...
  11. 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 ..
  12. REGULATION OF PLASMA CELL MALIGNANCY BY INSULIN AND IGF
    GREGORY FREUND; Fiscal Year: 1999
    ..Cellular responses included, phosphorylation of insulin receptor substrate-1 (IRS-1), activation of phosphatidylinositol 3- kinase (PI3-kinase), increased DNA synthesis and ..
  13. INSULIN DEGRADING ENZYMES AND THE INSULIN RECEPTOR
    Richard Roth; Fiscal Year: 1991
    The insulin receptor serves to focus the hormone on particular target tissues as well as to initiate the responses of these cells to the hormone...
  14. Alternative Splicing of the Insulin Receptor Gene
    NICHOLAS J WEBSTER; Fiscal Year: 2011
    ..There are two variants of the insulin receptor (IR), which differ in the presence of 12-amino acids in the hormone-binding domain...
  15. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2009
    ..Burn injury alters the insulin signaling pathway at multiple points, via the insulin receptor, insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3-K), Akt/PKB (protein kinase B), and ..
  16. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2010
    ..Burn injury alters the insulin signaling pathway at multiple points, via the insulin receptor, insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3-K), Akt/PKB (protein kinase B), and ..
  17. INSULIN RECEPTOR REGULATION BY PHOSPHORYLATION
    Robert Lewis; Fiscal Year: 1990
    Exposure of cells to insulin promotes phosphorylation of the insulin receptor's cytoplasmic domain on serine, threonine and tyrosine...
  18. MECHANISMS AND EFFECT OF DECREASED GLUCOSE INSULIN SENSITIVITY IN PREGNANT WOMEN
    Patrick Catalano; Fiscal Year: 1999
    ..gestation and postpartum, 2) to determine the role of tumor necrosis factor alpha (TNFalpha) modulation of insulin receptor beta (IRbeta) and insulin receptor substrate I (IRS-1) in skeletal muscle in late pregnancy and 3) to ..
  19. MECHANISMS AND EFFECT OF DECREASED GLUCOSE INSULIN SENSITIVITY IN PREGNANT WOMEN
    Patrick Catalano; Fiscal Year: 2000
    ..gestation and postpartum, 2) to determine the role of tumor necrosis factor alpha (TNFalpha) modulation of insulin receptor beta (IRbeta) and insulin receptor substrate I (IRS-1) in skeletal muscle in late pregnancy and 3) to ..
  20. MECHANISMS AND EFFECT OF DECREASED GLUCOSE INSULIN SENSITIVITY IN PREGNANT WOMEN
    Patrick Catalano; Fiscal Year: 2001
    ..gestation and postpartum, 2) to determine the role of tumor necrosis factor alpha (TNFalpha) modulation of insulin receptor beta (IRbeta) and insulin receptor substrate I (IRS-1) in skeletal muscle in late pregnancy and 3) to ..
  21. MOLECULAR REGULATION OF MUSCLE GLUCOSE METABOLISM IN MAN
    Lawrence Mandarino; Fiscal Year: 2003
    ..The insulin receptor signaling system is a likely focus of insulin resistance...
  22. MOLECULAR REGULATION OF MUSCLE GLUCOSE METABOLISM IN MAN
    Lawrence Mandarino; Fiscal Year: 2002
    ..The insulin receptor signaling system is a likely focus of insulin resistance...
  23. MOLECULAR REGULATION OF MUSCLE GLUCOSE METABOLISM IN MAN
    Lawrence Mandarino; Fiscal Year: 2005
    ..The insulin receptor signaling system is a likely focus of insulin resistance...
  24. MOLECULAR REGULATION OF MUSCLE GLUCOSE METABOLISM IN MAN
    Lawrence Mandarino; Fiscal Year: 2004
    ..The insulin receptor signaling system is a likely focus of insulin resistance...
  25. MOLECULAR REGULATION OF MUSCLE GLUCOSE METABOLISM IN MAN
    Lawrence Mandarino; Fiscal Year: 2004
    ..The insulin receptor signaling system is a likely focus of insulin resistance...
  26. MOLECULAR REGULATION OF MUSCLE GLUCOSE METABOLISM IN MAN
    Lawrence Mandarino; Fiscal Year: 2002
    ..The insulin receptor signaling system is a likely focus of insulin resistance...
  27. MOLECULAR REGULATION OF MUSCLE GLUCOSE METABOLISM IN MAN
    Lawrence Mandarino; Fiscal Year: 2003
    ..The insulin receptor signaling system is a likely focus of insulin resistance...
  28. TNF RECEPTOR FUNCTION IN INSULIN RESISTANCE AND OBESITY
    GOKHAN HOTAMISLIGIL; Fiscal Year: 2002
    ..TNFa interferes with insulin action by inhibiting the tyrosine kinase activity of the insulin receptor (IR) both in cultured cells and in whole animals...
  29. TNF RECEPTOR FUNCTION IN INSULIN RESISTANCE AND OBESITY
    GOKHAN HOTAMISLIGIL; Fiscal Year: 2001
    ..TNFa interferes with insulin action by inhibiting the tyrosine kinase activity of the insulin receptor (IR) both in cultured cells and in whole animals...
  30. TNF RECEPTOR FUNCTION IN INSULIN RESISTANCE AND OBESITY
    GOKHAN HOTAMISLIGIL; Fiscal Year: 2003
    ..TNFa interferes with insulin action by inhibiting the tyrosine kinase activity of the insulin receptor (IR) both in cultured cells and in whole animals...
  31. TNF RECEPTOR FUNCTION IN INSULIN RESISTANCE AND OBESITY
    GOKHAN HOTAMISLIGIL; Fiscal Year: 2004
    ..TNFa interferes with insulin action by inhibiting the tyrosine kinase activity of the insulin receptor (IR) both in cultured cells and in whole animals...
  32. TNF RECEPTOR FUNCTION IN INSULIN RESISTANCE AND OBESITY
    GOKHAN HOTAMISLIGIL; Fiscal Year: 2003
    ..TNFa interferes with insulin action by inhibiting the tyrosine kinase activity of the insulin receptor (IR) both in cultured cells and in whole animals...
  33. PTEN TUMOR SUPPRESSOR AND SIGNAL TRANSDUCTION
    Ramon Parsons; Fiscal Year: 2001
    ..influence many signaling pathways, perhaps the best understood pathway species, PTEN acts downstream of the insulin receptor and PI-3 kinase and upstream of AKT...
  34. PTEN TUMOR SUPPRESSOR AND SIGNAL TRANSDUCTION
    Ramon Parsons; Fiscal Year: 2003
    ..influence many signaling pathways, perhaps the best understood pathway species, PTEN acts downstream of the insulin receptor and PI-3 kinase and upstream of AKT...
  35. PTEN TUMOR SUPPRESSOR AND SIGNAL TRANSDUCTION
    Ramon Parsons; Fiscal Year: 2002
    ..influence many signaling pathways, perhaps the best understood pathway species, PTEN acts downstream of the insulin receptor and PI-3 kinase and upstream of AKT...
  36. PTEN TUMOR SUPPRESSOR AND SIGNAL TRANSDUCTION
    Ramon Parsons; Fiscal Year: 2005
    ..influence many signaling pathways, perhaps the best understood pathway species, PTEN acts downstream of the insulin receptor and PI-3 kinase and upstream of AKT...
  37. PTEN TUMOR SUPPRESSOR AND SIGNAL TRANSDUCTION
    Ramon Parsons; Fiscal Year: 2004
    ..influence many signaling pathways, perhaps the best understood pathway species, PTEN acts downstream of the insulin receptor and PI-3 kinase and upstream of AKT...
  38. Role of IGF-1 and insulin receptors beta-cell survival
    Rohit Kulkarni; Fiscal Year: 2006
    ..this question mouse models with beta-cell-specific ablation of either the IGF-1 receptor (betaIGFKO) or the insulin receptor (betaIRKO) have been created...
  39. Role of IGF-1 and insulin receptors beta-cell survival
    Rohit Kulkarni; Fiscal Year: 2004
    ..this question mouse models with beta-cell-specific ablation of either the IGF-1 receptor (betaIGFKO) or the insulin receptor (betaIRKO) have been created...
  40. Role of IGF-1 and insulin receptors beta-cell survival
    Rohit Kulkarni; Fiscal Year: 2005
    ..this question mouse models with beta-cell-specific ablation of either the IGF-1 receptor (betaIGFKO) or the insulin receptor (betaIRKO) have been created...
  41. Role of IGF-1 and insulin receptors beta-cell survival
    Rohit Kulkarni; Fiscal Year: 2007
    ..this question mouse models with beta-cell-specific ablation of either the IGF-1 receptor (betaIGFKO) or the insulin receptor (betaIRKO) have been created...
  42. TNF RECEPTOR FUNCTION IN INSULIN RESISTANCE AND OBESITY
    GOKHAN HOTAMISLIGIL; Fiscal Year: 2005
    ..TNFa interferes with insulin action by inhibiting the tyrosine kinase activity of the insulin receptor (IR) both in cultured cells and in whole animals...
  43. INSULIN RECEPTOR STRUCTURE AND TURNOVER
    C Ronald Kahn; Fiscal Year: 2010
    ..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 ..
  44. INSULIN AND PROSTACYCLIN IN ISCHEMIC HEART DISEASE
    ASRU SINHA; Fiscal Year: 1990
    ....
  45. 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...
  46. ARF PROTEINS IN CELLULAR REGULATION OF PHOSPHOLIPASE D
    Guillermo Romero; Fiscal Year: 1999
    ..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...
  47. 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 ..
  48. REGULATION OF LIVER GROWTH AND FUNCTION
    Leonard S Jefferson; Fiscal Year: 2010
    ..The nutrient-sensing pathways are not only interconnected at multiple levels but are tightly coupled to the insulin receptor signaling pathway...
  49. Targeting crosstalk between insulin and Gq signaling systems in pancreatic cancer
    JUAN ROZENGURT; Fiscal Year: 2009
    ..Crosstalk between the insulin receptor and G protein-coupled receptor (GPCR) signaling systems plays a critical role in the regulation of many ..
  50. 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...
  51. MOLECULAR COMPONENTS OF INSULIN RECEPTOR BIOGENESIS
    Joseph Bass; Fiscal Year: 2002
    ..Insulin resistance is a predisposing factor for diabetes and can be induced by impaired biogenesis of the insulin receptor, a transmembrane protein tyrosine kinase...
  52. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin Devaskar; Fiscal Year: 2007
    ..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 ..
  53. PGC-1 and Muscle Mitochondrial Dysfunction in Diabetes
    Lawrence Mandarino; Fiscal Year: 2007
    ..intramyocellular lipids, including triglycerides, fatty acids (FFA), fatty acyI-CoAs, and ceramides inhibit insulin receptor signaling and cause insulin resistance...
  54. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin Devaskar; Fiscal Year: 2009
    ..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 ..
  55. Regulation of Retinal Cell Death in Diabetes
    THOMAS W contact GARDNER; Fiscal Year: 2010
    ..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 ..
  56. 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 ..
  57. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin Devaskar; Fiscal Year: 2009
    ..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 ..
  58. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin Devaskar; Fiscal Year: 2006
    ..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 ..
  59. PGC-1 and Muscle Mitochondrial Dysfunction in Diabetes
    Lawrence Mandarino; Fiscal Year: 2006
    ..intramyocellular lipids, including triglycerides, fatty acids (FFA), fatty acyI-CoAs, and ceramides inhibit insulin receptor signaling and cause insulin resistance...
  60. PGC-1 and Muscle Mitochondrial Dysfunction in Diabetes
    Lawrence Mandarino; Fiscal Year: 2004
    ..intramyocellular lipids, including triglycerides, fatty acids (FFA), fatty acyI-CoAs, and ceramides inhibit insulin receptor signaling and cause insulin resistance...
  61. PGC-1 and Muscle Mitochondrial Dysfunction in Diabetes
    Lawrence Mandarino; Fiscal Year: 2005
    ..intramyocellular lipids, including triglycerides, fatty acids (FFA), fatty acyI-CoAs, and ceramides inhibit insulin receptor signaling and cause insulin resistance...
  62. PROPERTIES OF THE HIGH AFFINITY INSULIN RECEPTOR
    Michael Czech; Fiscal Year: 1991
    ..Major accomplishments have included elucidation of insulin receptor and IGF-I receptor tyrosine kinase regulation by tyrosine phosphorylation in vitro and in vivo, and isolation ..
  63. PROPERTIES OF THE HIGH AFFINITY INSULIN RECEPTOR
    Michael Czech; Fiscal Year: 1990
    ..Major accomplishments have included elucidation of insulin receptor and IGF-I receptor tyrosine kinase regulation by tyrosine phosphorylation in vitro and in vivo, and isolation ..
  64. PROPERTIES OF THE HIGH AFFINITY INSULIN RECEPTOR
    Michael Czech; Fiscal Year: 1992
    ..Major accomplishments have included elucidation of insulin receptor and IGF-I receptor tyrosine kinase regulation by tyrosine phosphorylation in vitro and in vivo, and isolation ..
  65. PROTEIN-LIPID INTERACTIONS IN SIGNAL TRANSDUCTION
    ALEXANDRA NEWTON; Fiscal Year: 1990
    ..protein:lipid interactions in the processing of information by the lipid-dependent protein kinase C and the insulin receptor will be investigated...
  66. SUBSTRATES FOR THE INSULIN RECEPTOR TYROSINE KINASE
    David Lebwohl; Fiscal Year: 1990
    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...
  67. INSULIN RECEPTOR SIGNALLING
    Ira Goldfine; Fiscal Year: 1991
    The insulin receptor is a alpha2beta2 tetrameric protein having an extracellular alpha subunit with an insulin binding domain and a transmembrane beta subunit with an intracellular tyrosine kinase domain...
  68. MOLECULAR COMPONENENTS OF INSULIN RECEPTOR BIOGENESIS
    Joseph Bass; Fiscal Year: 2001
    ..and Graeme Bell at the University of Chicago where he investigated the biosynthesis and structure of the insulin receptor. This work provided the foundation for the present application...
  69. 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...
  70. MOLECULAR COMPONENENTS OF INSULIN RECEPTOR BIOGENESIS
    Joseph Bass; Fiscal Year: 2002
    ..and Graeme Bell at the University of Chicago where he investigated the biosynthesis and structure of the insulin receptor. This work provided the foundation for the present application...
  71. MOLECULAR COMPONENTS OF INSULIN RECEPTOR BIOGENESIS
    Joseph Bass; Fiscal Year: 1999
    ..and Graeme Bell at the University of Chicago where he investigated the biosynthesis and structure of the insulin receptor. This work provided the foundation for the present application...
  72. MOLECULAR COMPONENENTS OF INSULIN RECEPTOR BIOGENESIS
    Joseph Bass; Fiscal Year: 2000
    ..and Graeme Bell at the University of Chicago where he investigated the biosynthesis and structure of the insulin receptor. This work provided the foundation for the present application...
  73. MOLECULAR COMPONENTS OF INSULIN RECEPTOR BIOGENESIS
    Joseph Bass; Fiscal Year: 1999
    ..and Graeme Bell at the University of Chicago where he investigated the biosynthesis and structure of the insulin receptor. This work provided the foundation for the present application...
  74. INSULIN RECEPTOR RELATED RECEPTOR
    Richard Roth; Fiscal Year: 1992
    ..Hence, it was given the name insulin receptor-related receptor (or IRR)...