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 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
  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 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
  5. 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
  6. ncbi 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
  7. 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
  8. 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
  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 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

Research Grants

  1. PATHOGENESIS, IMMUNODIAGNOSIS AND THERAPY OF HCC
    Jack Wands; Fiscal Year: 2007
  2. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2005
  3. Role of Insulin Receptors in the Kidney
    CAROLYN MARY ECELBARGER; Fiscal Year: 2010
  4. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2010
  5. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2009
  6. MOLECULAR PHARMACOLOGY OF INSULIN RESISTANCE IN BURNS
    JEEVENDRA MARTYN; Fiscal Year: 2010
  7. MOLECULAR REGULATION OF MUSCLE GLUCOSE METABOLISM IN MAN
    Lawrence Mandarino; Fiscal Year: 2005
  8. PTEN TUMOR SUPPRESSOR AND SIGNAL TRANSDUCTION
    Ramon Parsons; Fiscal Year: 2005
  9. Role of IGF-1 and insulin receptors beta-cell survival
    Rohit Kulkarni; Fiscal Year: 2007
  10. TNF RECEPTOR FUNCTION IN INSULIN RESISTANCE AND OBESITY
    GOKHAN HOTAMISLIGIL; Fiscal Year: 2005

Detail Information

Publications294 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 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...
  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 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...
  5. 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...
  6. ncbi 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 ..
  7. 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...
  8. 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...
  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 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...
  11. 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...
  12. 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.
  13. 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...
  14. ncbi 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...
  15. 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...
  16. 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...
  17. ncbi 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 ..
  18. 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...
  19. ncbi 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...
  20. ncbi 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 ..
  21. 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...
  22. 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 ..
  23. 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 ..
  24. 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
    ....
  25. 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...
  26. 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...
  27. ncbi 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...
  28. 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...
  29. 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...
  30. ncbi 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...
  31. 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...
  32. 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...
  33. 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...
  34. ncbi 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...
  35. 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
    ..We investigated the mechanisms of this improvement. DESIGN: Insulin receptor (IR) content, IR signaling, and adiponectin levels were measured in nine morbidly obese subjects before and ..
  36. 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...
  37. 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...
  38. 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...
  39. 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
  40. ncbi 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
    ....
  41. 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...
  42. 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...
  43. 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 ..
  44. 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...
  45. ncbi 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)...
  46. 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...
  47. ncbi 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...
  48. 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...
  49. 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...
  50. 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...
  51. ncbi 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...
  52. 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...
  53. ncbi 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)...
  54. ncbi 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 ..
  55. ncbi 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...
  56. ncbi Akt mediates the cross-talk between beta-adrenergic and insulin receptors in neonatal cardiomyocytes
    Carmine Morisco
    Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, , Napoli, Italy
    Circ Res 96:180-8. 2005
    ..receptors inhibits both insulin-stimulated glucose uptake and insulin-induced autophosphorylation of the insulin receptor, and at the same time promotes threonine phosphorylation of the insulin receptor...
  57. 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 ..
  58. ncbi Cold-induced PGC-1alpha expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway
    Rachel L G S Oliveira
    Department of Internal Medicine, State University of Campinas, SP 13083 970, Brazil
    Am J Physiol Endocrinol Metab 287:E686-95. 2004
    ..Cold exposure promoted significantly lower insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and Ser473 phosphorylation of acute transforming retrovirus thymoma (Akt) and an insulin-independent ..
  59. ncbi Secretion of Annexin II via activation of insulin receptor and insulin-like growth factor receptor
    Wei Qin Zhao
    Laboratory of Adaptive Systems, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 278:4205-15. 2003
    ..These results suggest that the insulin receptor and its signaling pathways may participate in molecular mechanisms mediating annexin II secretion.
  60. ncbi 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)...
  61. ncbi Two mutant alleles of the insulin receptor gene in a family with a genetic form of insulin resistance: a 10 base pair deletion in exon 1 and a mutation substituting serine for asparagine-462
    A Cama
    Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20892
    Hum Genet 95:174-82. 1995
    Mutations in the insulin receptor gene cause several genetic syndromes associated with extreme insulin resistance. We have studied three insulin resistant siblings with acanthosis nigricans, dental abnormalities, and acral hypertrophy...
  62. 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))...
  63. ncbi Interleukin-6 induces cellular insulin resistance in hepatocytes
    Joseph J Senn
    Graduate Program in Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Diabetes 51:3391-9. 2002
    ..Here, we present data that IL-6 can inhibit insulin receptor (IR) signal transduction and insulin action in both primary mouse hepatocytes and the human hepatocarcinoma ..
  64. ncbi A central role for JNK in obesity and insulin resistance
    Jiro Hirosumi
    Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA
    Nature 420:333-6. 2002
    ..an absence of JNK1 results in decreased adiposity, significantly improved insulin sensitivity and enhanced insulin receptor signalling capacity in two different models of mouse obesity...
  65. ncbi Reciprocal feedback regulation of insulin receptor and insulin receptor substrate tyrosine phosphorylation by phosphoinositide 3-kinase in primary adipocytes
    Ingeborg Hers
    Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK
    Biochem J 368:875-84. 2002
    Signalling by the insulin receptor substrate (IRS) proteins is critically dependent on the tyrosine phosphorylation of specific binding sites that recruit Src homology 2 (SH2)-domain-containing proteins, such as the p85 subunit of ..
  66. ncbi Atypical beta-adrenergic effects on insulin signaling and action in beta(3)-adrenoceptor-deficient brown adipocytes
    Petra Jost
    Department of Internal Medicine I, , , Germany
    Am J Physiol Endocrinol Metab 283:E146-53. 2002
    ..Stimulation with CGP-12177 did not impair insulin receptor kinase activity but decreased insulin receptor substrate-1 binding to phosphatidylinositol (PI) 3-kinase and ..
  67. ncbi Differential effects of tumor necrosis factor-alpha on protein kinase C isoforms alpha and delta mediate inhibition of insulin receptor signaling
    Tovit Rosenzweig
    Faculty of Life Sciences, Gonda Goldschmied Center, Bar Ilan University, Ramat Gan, Israel
    Diabetes 51:1921-30. 2002
    ..TNF-alpha, given 5 min before insulin, inhibited insulin-induced tyrosine phosphorylation of insulin receptor (IR), IR substrate (IRS)-1, insulin-induced association of IRS-1 with the p85 subunit of phosphatidylinositol ..
  68. ncbi Molecular insights into insulin action and secretion
    C J Rhodes
    Pacific Northwest Research Institute and Department of Pharmacology, University of Washington, 720 Broadway, Seattle, WA 98122, USA
    Eur J Clin Invest 32:3-13. 2002
    ..molecules that affect insulin action, including insulin and insulin-like growth factor-1 (IGF-1) receptors, insulin receptor substrate (IRS) proteins and various downstream effector proteins...
  69. ncbi 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...
  70. ncbi The role of glycogen synthase kinase-3 in insulin resistance and type 2 diabetes
    Oksana Kaidanovich
    Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel-Aviv University, Israel
    Expert Opin Ther Targets 6:555-61. 2002
    ..The fact that the function of two key targets of insulin action, glycogen synthase and insulin receptor substrate-1, are suppressed by GSK-3, as well as the fact that GSK-3 activity is higher in diabetic tissues, ..
  71. ncbi Delays in insulin signaling towards glucose disposal in human skeletal muscle
    T Grimmsmann
    Medizinische Klinik 1, , Ratzeburger Allee 160, , Germany
    J Endocrinol 172:645-51. 2002
    ..Although plasma insulin had reached 98% of its final concentration within 10 min, insulin receptor kinase (IRK) activity, p85 associated with insulin receptor substrate-1 (IRS-1), IRS-1-associated ..
  72. ncbi N-3 polyunsaturated fatty acids prevent the defect of insulin receptor signaling in muscle
    Mohammed Taouis
    Station de Recherches Avicoles, Institut National de la Recherche Agronomique Centre de Tours, 37380 Nouzilly, France
    Am J Physiol Endocrinol Metab 282:E664-71. 2002
    ..3 for n-3 rats), signs of insulin resistance. In liver, both diets (n-3 and n-6) significantly reduced insulin receptor (IR) number, IR and IR substrate (IRS)-1 tyrosine phosphorylation, and phosphatidylinositol (PI) 3'-kinase ..
  73. ncbi Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
    Sung Hee Um
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
    Nature 431:200-5. 2004
    ..on a high fat diet, levels of glucose and free fatty acids still rise in S6K1-deficient mice, resulting in insulin receptor desensitization...
  74. ncbi Elevated basal PI 3-kinase activity and reduced insulin signaling in sucrose-induced hepatic insulin resistance
    Michael J Pagliassotti
    Division of Endocrinology, Metabolism and Diabetes, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    Am J Physiol Endocrinol Metab 282:E170-6. 2002
    ..Western blot analysis revealed no significant differences in the amount of insulin receptor (IR), insulin receptor substrates-1 and -2 (IRS-1, IRS-2), and the p85 subunit of phosphatidylinositol (PI) 3-..
  75. ncbi Infusion of beta-endorphin improves insulin resistance in fructose-fed rats
    C-F Su
    Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan, ROC
    Horm Metab Res 36:571-7. 2004
    ..Insulin resistance in rats induced by excess fructose was associated with the impaired insulin receptor (IR), tyrosine autophosphorylation, and insulin receptor substrate (IRS)-1 protein content in addition to the ..
  76. ncbi Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes
    Umut Ozcan
    Department of Genetics and Complex Diseases, Harvard Medical School, Boston, MA 02115, USA
    Science 306:457-61. 2004
    ..This stress in turn leads to suppression of insulin receptor signaling through hyperactivation of c-Jun N-terminal kinase (JNK) and subsequent serine phosphorylation of ..
  77. ncbi Regulation of IRS-2 tyrosine phosphorylation in fasting and diabetes
    F A Rojas
    , FCM-UNICAMP, 13081-970, Campinas, SP, Brazil
    Mol Cell Endocrinol 183:63-9. 2001
    ..involves a series of alternative and complementary pathways created by the multiple substrates of the insulin receptor (IRS) and the various isoforms of the SH2 domain signaling molecules that can interact with substrate...
  78. ncbi [Insulin signaling: mechanisms altered in insulin resistance]
    Jacqueline Capeau
    INSERM U 402, Hopital Tenon, Faculte de Medecine Saint Antoine, Universite Pierre et Marie Curie, 27, rue Chaligny, 75571 Paris Cedex 12, Paris, France
    Med Sci (Paris) 19:834-9. 2003
    ..The insulin receptor exhibits a tyrosine-kinase activity which leads, first, to receptor autophosphorylation and then to tyrosine ..
  79. ncbi Reduction of protein tyrosine phosphatase 1B increases insulin-dependent signaling in ob/ob mice
    Rebecca J Gum
    Metabolic Disease Research, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Diabetes 52:21-8. 2003
    Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin receptor (IR) signal transduction and a drug target for treatment of type 2 diabetes...
  80. ncbi Insulin and IGF-1 increase mitogenesis and glucose metabolism in the multiple myeloma cell line, RPMI 8226
    G G Freund
    Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, NY 14642
    J Immunol 151:1811-20. 1993
    ..32 nM. The Kd of high affinity IGF-1 binding sites for IGF-1 was 0.89 nM. Insulin receptor autophosphorylation was maximum at 200 nM as was tyrosine phosphorylation of the 180-kDa cytosolic receptor ..
  81. 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...
  82. ncbi Selective ovary resistance to insulin signaling in women with polycystic ovary syndrome
    Xiao Ke Wu
    Department of Obstetrics and Gynecology, School of Clinical Medicine, Jinling Hospital of Nanjing University, Nanjing, China
    Fertil Steril 80:954-65. 2003
    ....
  83. ncbi Arsenite stimulated glucose transport in 3T3-L1 adipocytes involves both Glut4 translocation and p38 MAPK activity
    Merlijn Bazuine
    Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands
    Eur J Biochem 270:3891-903. 2003
    ..Arsenite did not activate early steps of the insulin receptor (IR)-signalling pathway and the response was insensitive to inhibition of phosphatidylinositol-3'-kinase (PI-..
  84. ncbi Skeletal muscle reprogramming by activation of calcineurin improves insulin action on metabolic pathways
    Jeffrey W Ryder
    Department of Physiology and Pharmacology, Section of Integrative Physiology, Karolinska Institutet, 17177 Stockholm, Sweden
    J Biol Chem 278:44298-304. 2003
    ..longus (EDL) muscles compared with wild-type mice, concomitant with increased protein expression of the insulin receptor, Akt, glucose transporter 4, and peroxisome proliferator-activated receptor-gamma co-activator 1...
  85. ncbi Morphine induces desensitization of insulin receptor signaling
    Yu Li
    Cell Signaling Technology, Inc, Beverly, Massachusetts, USA
    Mol Cell Biol 23:6255-66. 2003
    ..to influence glucose homeostasis, we investigated the hypothesis of direct cross talk between the MOR and the insulin receptor (IR) signaling cascades...
  86. ncbi Modulation of IR/PTP1B interaction and downstream signaling in insulin sensitive tissues of MSG-rats
    Aparecida Emiko Hirata
    Departamento de Clinica Medica, Faculdade de Ciencias Medicas, Universidade Estadual de Campinas, FCM UNICAMP, 13081 970 Campinas, SP, Brazil
    Life Sci 73:1369-81. 2003
    ..In 28-week-old-MSG rats there was an increase in IR/PTP1B interaction and reduced insulin signaling in liver, muscle and adipocytes, and a more pronounced insulin resistance...
  87. ncbi Transgenic overexpression of protein-tyrosine phosphatase 1B in muscle causes insulin resistance, but overexpression with leukocyte antigen-related phosphatase does not additively impair insulin action
    Janice M Zabolotny
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 279:24844-51. 2004
    ..Insulin-stimulated insulin receptor (IR) tyrosyl phosphorylation and phosphatidylinositol 3'-kinase activity were impaired by 35% and 40-60% in ..
  88. ncbi Impact of Src homology 2-containing inositol 5'-phosphatase 2 on the regulation of insulin signaling leading to protein synthesis in 3T3-L1 adipocytes cultured with excess amino acids
    Shihou Murakami
    Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930 0194, Japan
    Endocrinology 145:3215-23. 2004
    ....
  89. ncbi Bi-directional regulation of brown fat adipogenesis by the insulin receptor
    Amelia J Entingh
    Department of Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, Massachusetts 02215, USA
    J Biol Chem 278:33377-83. 2003
    ..and differentiation of adipocytes requires many components of the insulin signaling pathway, including the insulin receptor substrate IRS-1 and phosphatidylinositol 3-kinase (PI3K)...
  90. ncbi Growth factor receptor-binding protein 10 (Grb10) as a partner of phosphatidylinositol 3-kinase in metabolic insulin action
    Youping Deng
    Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202, USA
    J Biol Chem 278:39311-22. 2003
    ..We find mouse Grb10 to be a critical component of the insulin receptor (IR) signaling complex that provides a functional link between IR and p85 phosphatidylinositol (PI) 3-kinase ..
  91. ncbi Signaling effects of demethylasterriquinone B1, a selective insulin receptor modulator
    Nicholas J G Webster
    Department of Medicine 0673 University of California San Diego, 9500 Gilman Drive La Jolla, California 92093, USA
    Chembiochem 4:379-85. 2003
    ..The activities of DAQ B1 and over a dozen related structures were studied for insulin receptor (IR) and insulin receptor substrate-1 phosphorylation...
  92. ncbi Metformin enhances insulin signalling in insulin-dependent and-independent pathways in insulin resistant muscle cells
    Naresh Kumar
    Signal Transduction Research Laboratory, Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Punjab, India
    Br J Pharmacol 137:329-36. 2002
    ..Insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) was determined...
  93. ncbi Overexpression of plasma membrane-associated sialidase attenuates insulin signaling in transgenic mice
    Akinori Sasaki
    Division of Biochemistry, Miyagi Prefectural Cancer Center, Natori, Miyagi 981 1293, Japan
    J Biol Chem 278:27896-902. 2003
    ..As compared with the wild type, insulin-stimulated phosphorylation of the insulin receptor (IR) and insulin receptor substrate I was significantly reduced, and activities of phosphatidylinositol 3-..
  94. ncbi Ethanol feeding induces insulin resistance with enhanced PI 3-kinase activation
    Yukiko Onishi
    The Institute for Adult Diseases, Asahi Life Foundation, 1-9-14, Nishishinjuku, Shinjuku-ku, Tokyo, Japan
    Biochem Biophys Res Commun 303:788-94. 2003
    ..In addition, the insulin signaling step impaired by ethanol feeding is likely to be downstream from PI 3-kinase...
  95. ncbi Adapter protein with a pleckstrin homology (PH) and an Src homology 2 (SH2) domain (APS) and SH2-B enhance insulin-receptor autophosphorylation, extracellular-signal-regulated kinase and phosphoinositide 3-kinase-dependent signalling
    Zamal Ahmed
    Institute of Cell Signalling and School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK
    Biochem J 371:405-12. 2003
    ....
  96. ncbi Dual regulation of upstream binding factor 1 levels by IRS-1 and ERKs in IGF-1-receptor signaling
    Hongzhi Sun
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    J Cell Physiol 212:780-6. 2007
    ..Ectopic expression of insulin receptor substrate-1 (IRS-1) in these cells inhibits the down-regulation of UBF1...
  97. ncbi Irbesartan restores the in-vivo insulin signaling pathway leading to Akt activation in obese Zucker rats
    Marina C Muñoz
    Instituto de Química y Fisicoquímica Biológicas UBA CONICET, Facultad de Farmacia y Bioquimica, Buenos Aires, Argentina
    J Hypertens 24:1607-17. 2006
    ..we illustrated that obese Zucker rats (OZR) present increased serine 994 (Ser994) phosphorylation of hepatic insulin receptor, and this event seems to be implicated in the regulation of the intrinsic IRK in this model of insulin ..
  98. 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...
  99. ncbi Reduction of low molecular weight protein-tyrosine phosphatase expression improves hyperglycemia and insulin sensitivity in obese mice
    Sanjay K Pandey
    Metabolic Disease Program, Antisense Drug Discovery, Isis Pharmaceuticals, Carlsbad, CA 92008, USA
    J Biol Chem 282:14291-9. 2007
    ..ob/ob mice led to increased phosphorylation and activity of key insulin signaling intermediates, including insulin receptor-beta subunit, phosphatidylinositol 3-kinase, and Akt in response to insulin stimulation...
  100. ncbi Effects of caloric restriction on insulin pathway gene expression in the skeletal muscle and liver of normal and long-lived GHR-KO mice
    Michal M Masternak
    Departments of Internal Medicine and Physiology, Geriatrics Research, Southern Illinois University, School of Medicine, P O Box 19628, Springfield, IL 62794 9628, USA
    Exp Gerontol 40:679-84. 2005
    ..The results also show that improved insulin sensitivity in response to CR is not due to increased mRNA expression of the above genes in either normal or GHR-KO animals...
  101. ncbi Insulin resistance with enhanced insulin signaling in high-salt diet-fed rats
    T Ogihara
    Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan
    Diabetes 50:573-83. 2001
    ..of insulin resistance, high salt-fed rats showed enhanced insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1, IRS-2 (liver and muscle), and IRS-3 (liver only)...

Research Grants87

  1. PATHOGENESIS, IMMUNODIAGNOSIS AND THERAPY OF HCC
    Jack Wands; Fiscal Year: 2007
    ..During the last four years, we have made several significant observations: 1) the insulin receptor substrate-1 (IRS-1) signal transduction cascade plays a major role in hepatocyte proliferation...
  2. 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 ..
  3. 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 ..
  4. 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)...
  5. 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 ..
  6. 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 ..
  7. 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...
  8. 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...
  9. 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...
  10. 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...
  11. 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...
  12. 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...
  13. 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...
  14. 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 ..
  15. 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 ..
  16. 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 ..
  17. 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 ..
  18. 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 ..