Irs1

Summary

Gene Symbol: Irs1
Description: insulin receptor substrate 1
Alias: IRS1IRM, IRS-1, pp185
Species: rat

Top Publications

  1. ncbi Bradykinin augments insulin-stimulated glucose transport in rat adipocytes via endothelial nitric oxide synthase-mediated inhibition of Jun NH2-terminal kinase
    Kristin M Beard
    Department of Medicine and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X6
    Diabetes 55:2678-87. 2006
  2. pmc Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline
    Konrad Talbot
    Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 3403, USA
    J Clin Invest 122:1316-38. 2012
  3. ncbi Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle
    Chunli Yu
    Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 277:50230-6. 2002
  4. 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
  5. pmc Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading
    Reiko Nakao
    Department of Nutritional Physiology, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto Cho, Tokushima, Japan
    Mol Cell Biol 29:4798-811. 2009
  6. pmc Endotoxin mediated-iNOS induction causes insulin resistance via ONOO⁻ induced tyrosine nitration of IRS-1 in skeletal muscle
    Genevieve Pilon
    Department of Medicine, Quebec Heart and Lung Institute Laval Hospital, Ste Foy, Quebec, Canada
    PLoS ONE 5:e15912. 2010
  7. pmc Glomerular-specific protein kinase C-β-induced insulin receptor substrate-1 dysfunction and insulin resistance in rat models of diabetes and obesity
    Akira Mima
    Section of Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Kidney Int 79:883-96. 2011
  8. pmc Resistin promotes cardiac hypertrophy via the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) and c-Jun N-terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathways
    Soojeong Kang
    Cardiovascular Research Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 286:18465-73. 2011
  9. ncbi Aspirin inhibits serine phosphorylation of IRS-1 in muscle and adipose tissue of septic rats
    Guilherme C Barreiro
    Departamento de Clinica Medica, FCM, Universidade Estadual de Campinas UNICAMP, Campinas, SP, Brazil
    Biochem Biophys Res Commun 320:992-7. 2004
  10. ncbi Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
    X J Sun
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215
    Nature 352:73-7. 1991

Scientific Experts

  • Paramjit S Tappia
  • Bo Zhu
  • Konrad Talbot
  • Barry J Goldstein
  • Michael Merger
  • Maja Jensen
  • Yi Jiang
  • Hirofumi Hitomi
  • Mark E Cleasby
  • BENEDICT B YASPELKIS
  • Thomas L Hilder
  • RAJU RAJALA
  • Harold Franch
  • Gabriella Mincione
  • Jørgen Jensen
  • Najma Begum
  • M G Baroni
  • Mario J A Saad
  • Licio A Velloso
  • Pedro Geraldes
  • Leila Khamzina
  • Mirian Ueno
  • Jose R Pauli
  • Eduardo R Ropelle
  • Claudio T De Souza
  • Jose B C Carvalheira
  • Robert J Walker
  • Soojeong Kang
  • Thirupathi Muthusamy
  • Tokio Matsunami
  • Akira Mima
  • Aparecida Emiko Hirata
  • Adrienne S McCampbell
  • Michael A Kiraly
  • Guido T Bommer
  • Genevieve Pilon
  • Christian Rask-Madsen
  • George L King
  • Yuzuru Ohshiro
  • Amanda L Klein
  • Mauricio Dorfman
  • Tara L Archuleta
  • B T Bikman
  • Michael C Allemand
  • E Matthew Morris
  • Reiko Nakao
  • Shuang Wang
  • Erin L Glynn
  • Rizwana Sanaullah Waraich
  • Xi Lian Li
  • KAREN O'BRIEN
  • Andre Marette
  • Jin Ying Wang
  • Avia Herschkovitz
  • Yehiel Zick
  • Dennys E Cintra
  • Yechiel Levkovitz
  • Jorge F Giani
  • Karin G Stenkula
  • Denise Ronen
  • Sigrun R Hugl
  • Fumihiko Hakuno
  • Julio Sevillano
  • C D'Alessandris
  • Kristin M Beard
  • Shao Liang Zhou
  • Rainer Lehmann
  • Margarita Villar
  • Erwin D Schleicher
  • Hans Ulrich Haring
  • Ranmali Nawaratne
  • Pradeep P Kayampilly
  • Cora Weigert
  • Hubert Kalbacher
  • Wolfgang Voelter
  • Qi Fu
  • Patricia O Prada
  • T Johansen
  • Frida Renstrom
  • Seung Y Park
  • Jeong A Kim
  • Ziva Liberman
  • Antonio J Ruiz-Alcaraz
  • Yoshihiro Taniyama
  • Eliana P Araujo
  • Patrícia Oliveira Prada
  • Guilherme C Barreiro
  • Francesco Andreozzi
  • Ken ichiro Hayashi
  • Yunhua Li

Detail Information

Publications92

  1. ncbi Bradykinin augments insulin-stimulated glucose transport in rat adipocytes via endothelial nitric oxide synthase-mediated inhibition of Jun NH2-terminal kinase
    Kristin M Beard
    Department of Medicine and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X6
    Diabetes 55:2678-87. 2006
    ..These data indicate that bradykinin enhances insulin sensitivity in adipocytes via an NO-dependent pathway that acts by modulating the feedback inhibition of insulin signaling at the level of IRS-1...
  2. pmc Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline
    Konrad Talbot
    Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 3403, USA
    J Clin Invest 122:1316-38. 2012
    ....
  3. ncbi Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle
    Chunli Yu
    Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 277:50230-6. 2002
    ..This in turn leads to decreased IRS-1 tyrosine phosphorylation and decreased activation of IRS-1-associated PI3-kinase activity resulting in decreased insulin-stimulated glucose transport activity...
  4. 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
    ..in the iNOS protein level and S-nitrosation of insulin receptor beta (IR beta), insulin receptor substrate 1 (IRS1) and Akt...
  5. pmc Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading
    Reiko Nakao
    Department of Nutritional Physiology, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto Cho, Tokushima, Japan
    Mol Cell Biol 29:4798-811. 2009
    ..The inhibition of Cbl-b-mediated ubiquitination may be a new therapeutic strategy for unloading-mediated muscle atrophy...
  6. pmc Endotoxin mediated-iNOS induction causes insulin resistance via ONOO⁻ induced tyrosine nitration of IRS-1 in skeletal muscle
    Genevieve Pilon
    Department of Medicine, Quebec Heart and Lung Institute Laval Hospital, Ste Foy, Quebec, Canada
    PLoS ONE 5:e15912. 2010
    ..Here we examined the role of inducible nitric oxide synthase (iNOS) in skeletal muscle insulin resistance using LPS challenge in rats and mice as in vivo models of endotoxemia...
  7. pmc Glomerular-specific protein kinase C-β-induced insulin receptor substrate-1 dysfunction and insulin resistance in rat models of diabetes and obesity
    Akira Mima
    Section of Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Kidney Int 79:883-96. 2011
    ..with nondiabetic and Zucker lean rats, the insulin-induced phosphorylation of insulin receptor substrate-1 (IRS1), Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3α were selectively inhibited in the ..
  8. pmc Resistin promotes cardiac hypertrophy via the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) and c-Jun N-terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathways
    Soojeong Kang
    Cardiovascular Research Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 286:18465-73. 2011
    ..Furthermore, resistin increased serine phosphorylation of insulin receptor substrate (IRS1) through the activation of the apoptosis signal-regulating kinase 1/c-Jun N-terminal Kinase (JNK) pathway, a module ..
  9. ncbi Aspirin inhibits serine phosphorylation of IRS-1 in muscle and adipose tissue of septic rats
    Guilherme C Barreiro
    Departamento de Clinica Medica, FCM, Universidade Estadual de Campinas UNICAMP, Campinas, SP, Brazil
    Biochem Biophys Res Commun 320:992-7. 2004
    ..Overall, these results provide important new insights into the mechanism of sepsis-induced insulin resistance...
  10. ncbi Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
    X J Sun
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215
    Nature 352:73-7. 1991
    ..tyrosine phosphorylation of a protein of relative molecular mass between 165,000 and 185,000, collectively called pp185, showed that the insulin receptor kinase has specific cellular substrates...
  11. pmc Oxidant stress-induced loss of IRS-1 and IRS-2 proteins in rat skeletal muscle: role of p38 MAPK
    Tara L Archuleta
    Muscle Metabolism Laboratory, Department of Physiology, University of Arizona College of Medicine, Tucson, AZ 85721 0093, USA
    Free Radic Biol Med 47:1486-93. 2009
    ....
  12. ncbi Role of insulin receptor substrate-1 serine 307 phosphorylation and adiponectin in adipose tissue insulin resistance in late pregnancy
    Julio Sevillano
    Facultad de Farmacia, Universidad CEU San Pablo, Crta Boadilla Km 5, 3, Madrid, Spain
    Endocrinology 148:5933-42. 2007
    ..Together, our findings support a role for adiponectin and serine phosphorylation of IRS-1 in the modulation of insulin resistance in adipose tissue at late pregnancy...
  13. ncbi Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance
    Leila Khamzina
    Department of Anantomy and Physiology and Lipid Research Unit, Laval University Hospital Research Center, 2705 Laurier Boulevard, Ste Foy, Quebec, Canada G1V 4G2
    Endocrinology 146:1473-81. 2005
    ..In vitro studies with rapamycin suggest that mTOR/S6K1 overactivation contributes to elevated serine phosphorylation of IRS-1, leading to impaired insulin signaling to Akt in liver and muscle of this dietary model of obesity...
  14. ncbi Nuclear matrix association of insulin receptor and IRS-1 by insulin in osteoblast-like UMR-106 cells
    Ki Cheon Seol
    Department of Pharmacology, School of Dentistry, Kyung Hee University, Seoul 130 701, Republic of Korea
    Biochem Biophys Res Commun 306:898-904. 2003
    ..The nuclear insulin signaling may play an important role in the transcription control, differentiation, and growth of osteoblast cells...
  15. pmc The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling
    E Y Skolnik
    New York University Medical Center, Department of Pharmacology, NY 10016
    EMBO J 12:1929-36. 1993
    ..These interactions may play a crucial role in activation of p21ras and the control of downstream effector molecules...
  16. pmc Silencing of insulin receptor substrate-1 increases cell death in retinal Müller cells
    Robert J Walker
    Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA
    Mol Vis 18:271-9. 2012
    ..To determine whether β-adrenergic receptors require insulin receptor substrate (IRS)-1 activity to regulate apoptosis in retinal Müller cells...
  17. ncbi Activation of the hexosamine pathway leads to phosphorylation of insulin receptor substrate-1 on Ser307 and Ser612 and impairs the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin insulin biosynthetic pathway in RIN pancreatic beta-cells
    Francesco Andreozzi
    Dipartimento di Medicina Sperimentale e Clinica, Università di Catanzaro Magna Graecia, Via Tommaso Campanella, 115, 88100 Catanzaro, Italy
    Endocrinology 145:2845-57. 2004
    ..These changes result in impaired coupling of IRS-1 and PI 3-kinase, and activation of the Akt/mammalian target of rapamycin/phosphorylated heat- and acid-stable protein-1/p70S6 kinase pathway...
  18. ncbi Mechanisms of reactive oxygen species-dependent downregulation of insulin receptor substrate-1 by angiotensin II
    Yoshihiro Taniyama
    Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Arterioscler Thromb Vasc Biol 25:1142-7. 2005
    ..Therefore, we examined the effects of chronic angiotensin II treatment on IRS-1 phosphorylation and protein expression in vascular smooth muscle cells (VSMCs)...
  19. doi Loss of inhibitory insulin receptor substrate-1 phosphorylation is an early event in mammalian target of rapamycin-dependent endometrial hyperplasia and carcinoma
    Adrienne S McCampbell
    Department of Pathology, Science Park Research Division, The University of Texas M D Anderson Cancer Center, 1808 Park Road 1C, Smithville, TX 78957, USA
    Cancer Prev Res (Phila) 3:290-300. 2010
    ....
  20. ncbi Regulation of IRS-1/SHP2 interaction and AKT phosphorylation in animal models of insulin resistance
    Maria Helena M Lima
    Department of Internal Medicine, State University of Campinas, SP, Brazil
    Endocrine 18:1-12. 2002
    ....
  21. pmc High-fat feeding increases insulin receptor and IRS-1 coimmunoprecipitation with SOCS-3, IKKalpha/beta phosphorylation and decreases PI-3 kinase activity in muscle
    Ben B Yaspelkis
    Exercise Biochemistry Laboratory, Department of Kinesiology, California State University Northridge, Northridge, 18111 Nordhoff St, Northridge, CA 91330 8287 USA
    Am J Physiol Regul Integr Comp Physiol 296:R1709-15. 2009
    ....
  22. doi Exercise maintains euglycemia in association with decreased activation of c-Jun NH2-terminal kinase and serine phosphorylation of IRS-1 in the liver of ZDF rats
    Michael A Kiraly
    Dept of Physiology, Univ of Toronto, ON, Canada
    Am J Physiol Endocrinol Metab 298:E671-82. 2010
    ..These changes in oxidative stress markers and inflammation are associated with decreased hyperglycemia and insulin resistance and reduced expression of the main gluconeogenic enzyme phosphoenolpyruvate carboxykinase...
  23. pmc O-linked N-acetylglucosamine modification of insulin receptor substrate-1 occurs in close proximity to multiple SH2 domain binding motifs
    Amanda L Klein
    Department of Molecular and Cellular Pharmacology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Mol Cell Proteomics 8:2733-45. 2009
    ..These findings suggest that O-GlcNAc modification represents an additional layer of posttranslational regulation that may impact the specificity of effects elicited by insulin and IGF-1...
  24. ncbi Association studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onset
    Eleftheria Zeggini
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
    Diabetes 53:3319-22. 2004
    The gene encoding insulin receptor substrate-1 (IRS1) represents a strong biological candidate for a contributory role in type 2 diabetes susceptibility...
  25. ncbi Insulin receptor substrate-1/SHP-2 interaction, a phenotype-dependent switching machinery of insulin-like growth factor-I signaling in vascular smooth muscle cells
    Ken ichiro Hayashi
    Department of Neuroscience D13, Osaka University Graduate School of Medicine, Yamadaoka 2 2, Suita, Osaka 565 0871, Japan
    J Biol Chem 279:40807-18. 2004
    ....
  26. pmc A novel regulation of IRS1 (insulin receptor substrate-1) expression following short term insulin administration
    Antonio J Ruiz-Alcaraz
    Division of Pathology and Neurosciences, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Biochem J 392:345-52. 2005
    ..Attention has focused on early signalling events such as defective tyrosine phosphorylation of IRS1 (insulin receptor substrate-1), a major target for the insulin receptor tyrosine kinase...
  27. ncbi Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action
    Vincent Aguirre
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 277:1531-7. 2002
    ..These results suggest that inhibition of PTB domain function in IRS-1 by phosphorylation of Ser(307) (Ser(312) in human IRS-1) might be a general mechanism to regulate insulin signaling...
  28. pmc Reversal of diet-induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS-1 serine phosphorylation
    Eduardo R Ropelle
    Departamento de Clinica, Medica, FCM UNICAMP, Cidade Universitaria Zeferino Vaz, Campinas, Sao Paulo, Brazil, 13081 970
    J Physiol 577:997-1007. 2006
    ..Thus, acute exercise increased the insulin sensitivity during high-fat feeding in obese rats. Overall, these results provide new insights into the mechanism by which exercise restores insulin sensitivity...
  29. ncbi Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistance
    R A Mooney
    Department of Pathology, University of Rochester School of Medicine, Rochester, New York 14642, USA
    J Biol Chem 276:25889-93. 2001
    ..These results suggest that SOCS proteins may be inhibitors of IR signaling and could mediate cytokine-induced insulin resistance and contribute to the pathogenesis of type II diabetes...
  30. ncbi Regulation of insulin receptor substrate 1 pleckstrin homology domain by protein kinase C: role of serine 24 phosphorylation
    Ranmali Nawaratne
    Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, UK
    Mol Endocrinol 20:1838-52. 2006
    ..Several phosphoserine sites on IRS1 have been identified; the majority are located proximal to the phosphotryosine-binding domain or near key receptor ..
  31. ncbi Phosphorylation of Ser24 in the pleckstrin homology domain of insulin receptor substrate-1 by Mouse Pelle-like kinase/interleukin-1 receptor-associated kinase: cross-talk between inflammatory signaling and insulin signaling that may contribute to insulin
    Jeong A Kim
    Diabetes Unit, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 280:23173-83. 2005
    ....
  32. ncbi Functional studies of Akt isoform specificity in skeletal muscle in vivo; maintained insulin sensitivity despite reduced insulin receptor substrate-1 expression
    Mark E Cleasby
    Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
    Mol Endocrinol 21:215-28. 2007
    ..These data indicate distinct roles for Akt-1 and Akt-2 in muscle glucose metabolism and that moderate reductions in IRS-1 expression do not result in the development of insulin resistance in skeletal muscle in vivo...
  33. doi Adrenaline potentiates insulin-stimulated PKB activation in the rat fast-twitch epitrochlearis muscle without affecting IRS-1-associated PI 3-kinase activity
    Jørgen Jensen
    Department of Physiology, National Institute of Occupational Health, P O Box 8149 Dep, Oslo, 0033, Norway
    Pflugers Arch 456:969-78. 2008
    ..These results indicate that the combination of adrenaline and insulin may activate novel signalling molecules rather than just summing up their effects on linear pathways...
  34. doi Phosphorylation of Ser357 of rat insulin receptor substrate-1 mediates adverse effects of protein kinase C-delta on insulin action in skeletal muscle cells
    Rizwana Sanaullah Waraich
    Division of Clinical Chemistry and Pathobiochemistry, University of Tuebingen, Tuebingen, Germany
    J Biol Chem 283:11226-33. 2008
    ..Together, these data suggest that phosphorylation of Ser(357) mediates at least in part the adverse effects of PKC-delta activation on insulin action...
  35. ncbi 53BP2S, interacting with insulin receptor substrates, modulates insulin signaling
    Fumihiko Hakuno
    Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan
    J Biol Chem 282:37747-58. 2007
    ..Together these data demonstrate that 53BP2S interacts and modulates the insulin signals mediated by IRSs...
  36. doi Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model
    Tokio Matsunami
    Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa 252 0880, Japan
    Metabolism 60:805-14. 2011
    ..Thus, AdipoR and IRS might be crucially important regulators for the synthesis and oxidation of fatty acids in the liver of NASH...
  37. ncbi Antidepressants induce cellular insulin resistance by activation of IRS-1 kinases
    Yechiel Levkovitz
    Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Rabin Campus, Petah Tiqva, Israel
    Mol Cell Neurosci 36:305-12. 2007
    ..These results implicate selected SSRIs as inhibitors of insulin signaling and as potential inducers of cellular insulin resistance...
  38. ncbi Aldosterone suppresses insulin signaling via the downregulation of insulin receptor substrate-1 in vascular smooth muscle cells
    Hirofumi Hitomi
    Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kita gun, Japan
    Hypertension 50:750-5. 2007
    ....
  39. ncbi Common inhibitory serine sites phosphorylated by IRS-1 kinases, triggered by insulin and inducers of insulin resistance
    Avia Herschkovitz
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Faculty of Agricultural, Food, and Environmental Quality, The Hebrew University of Jerusalem, Rehovot, Israel
    J Biol Chem 282:18018-27. 2007
    ..These findings suggest that insulin-stimulated IRS kinases such as PKCzeta overlap with IRS kinases triggered by inducers of insulin resistance, such as IKKbeta, to phosphorylate IRS-1 on common Ser sites...
  40. ncbi C-reactive protein induces phosphorylation of insulin receptor substrate-1 on Ser307 and Ser 612 in L6 myocytes, thereby impairing the insulin signalling pathway that promotes glucose transport
    C D'Alessandris
    Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy
    Diabetologia 50:840-9. 2007
    ..However, it is unknown whether CRP directly affects insulin signalling action. To this aim, we determined the effects of human recombinant CRP (hrCRP) on insulin signalling involved in glucose transport in L6 myotubes...
  41. pmc A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle
    Erin L Glynn
    Division of Rehabilitation Sciences, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 1144, USA
    Appl Physiol Nutr Metab 33:93-101. 2008
    ....
  42. pmc beta-arrestin-1 competitively inhibits insulin-induced ubiquitination and degradation of insulin receptor substrate 1
    Isao Usui
    Department of Medicine 0673, University of California, San Diego, Stein Bldg, Room 210, 9500 Gilman Dr, La Jolla, CA 92093 0673, USA
    Mol Cell Biol 24:8929-37. 2004
    ....
  43. ncbi Regulation of insulin receptor substrate-1 in the liver, skeletal muscle and adipose tissue of rats throughout pregnancy
    C Gonzalez
    Department of Functional Biology, Physiology Area, University of Oviedo, c Julian Claveria s n, 33006 Oviedo, Spain
    Gynecol Endocrinol 17:187-97. 2003
    ....
  44. ncbi TGF-beta 1 modulation of IGF-I signaling pathway in rat thyroid epithelial cells
    Gabriella Mincione
    Dipartimento di Oncologia e Neuroscienze, Facolta di Medicina e Chirurgia, Universita G D Annunzio, Via dei Vestini, 31, Chieti, Italy
    Exp Cell Res 287:411-23. 2003
    ..Taken together, these findings provide a molecular basis for the growth-inhibitory action of TGF-beta 1 on the IGF-I-induced mitogenic effect...
  45. ncbi A novel T608R missense mutation in insulin receptor substrate-1 identified in a subject with type 2 diabetes impairs metabolic insulin signaling
    Diana L Esposito
    Department of Oncology and Neurosciences, Section of Molecular Pathology, University Gabriele D Annunzio, 66013 Chieti, Italy
    J Clin Endocrinol Metab 88:1468-75. 2003
    ..Interestingly, when cells transfected with IRS1-T608R were stimulated with insulin, both the amount of p85 coimmunoprecipitated with IRS1-T608R as well as the ..
  46. ncbi Protein kinase C-zeta-induced phosphorylation of Ser318 in insulin receptor substrate-1 (IRS-1) attenuates the interaction with the insulin receptor and the tyrosine phosphorylation of IRS-1
    Klaus Moeschel
    Department of Internal Medicine IV, Endocrinology, Metabolism, Pathobiochemistry and Clinical Chemistry, University Hospital Tubingen, D 72076 Tubingen, Germany
    J Biol Chem 279:25157-63. 2004
    ..These results, generated in BHK(IR) cells, suggest that phosphorylation of Ser(318) by PKC-zeta might contribute to the inhibitory effect of prolonged hyperinsulinemia on IRS-1 function...
  47. ncbi Acidosis impairs insulin receptor substrate-1-associated phosphoinositide 3-kinase signaling in muscle cells: consequences on proteolysis
    Harold A Franch
    Renal Divisioin, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    Am J Physiol Renal Physiol 287:F700-6. 2004
    ..We conclude that acidosis accelerates protein degradation by impairing insulin signaling through PI3K in muscle cells...
  48. ncbi Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells
    Luciano Pirola
    INSERM U145, IFR50, Faculte de Medecine, 06107 Nice Cedex 2, France
    J Biol Chem 278:15641-51. 2003
    ..In conclusion, the reduction in IRS proteins via different PI3K-mediated mechanisms contributes to the development of an insulin-resistant state in L6 myoblasts...
  49. ncbi In vivo phosphorylation of insulin receptor substrate 1 at serine 789 by a novel serine kinase in insulin-resistant rodents
    Li Ya Qiao
    Endocrinology Division, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA
    J Biol Chem 277:26530-9. 2002
    ..Taken together, these data strongly suggest that unknown serine kinase activity and Ser(789) phosphorylation of IRS-1 may play an important role in attenuating insulin signaling in insulin-resistant animal models...
  50. pmc SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin
    Chaojun Duan
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor 48109 0622, USA
    J Biol Chem 279:43684-91. 2004
    ..protein, promotes activation of the PI 3-kinase pathway by recruiting insulin receptor substrate 1 (IRS1) and IRS2 in response to leptin...
  51. ncbi Insulin signaling through insulin receptor substrate 1 and 2 in normal liver development
    Leila Khamzina
    Liver Research Center, Department of Medicine, Rhode Island Hospital and Brown Medical School, Providence, Rhode Island, USA
    Gastroenterology 125:572-85. 2003
    ..The purpose of this study was to determine the roles of the insulin receptor substrate (IRS-1 and IRS-2)-mediated growth cascades in rapidly growing fetal rat liver...
  52. ncbi Insulin resistance: interactions between obesity and a common variant of insulin receptor substrate-1
    J O Clausen
    Steno Diabetes Center, Gentofte, Denmark
    Lancet 346:397-402. 1995
    ..0008). Our results suggest that the codon-972 IRS-1 gene variant may interact with obesity in the pathogenesis of common insulin-resistant disorders...
  53. ncbi Serine 332 phosphorylation of insulin receptor substrate-1 by glycogen synthase kinase-3 attenuates insulin signaling
    Ziva Liberman
    Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    J Biol Chem 280:4422-8. 2005
    ..In summary, our studies identify Ser332 as the GSK-3 phosphorylation target in IRS-1, indicating its physiological relevance and demonstrating its novel inhibitory role in insulin signaling...
  54. ncbi Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein
    B J Goldstein
    Dorrance H Hamilton Research Laboratories, Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 275:4283-9. 2000
    ....
  55. pmc Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulation
    J M Backer
    Joslin Diabetes Center, Department of Medicine, Brigham and Women s Hospital, Boston, MA
    EMBO J 11:3469-79. 1992
    ..We conclude that the binding of tyrosyl phosphorylated IRS-1 to the SH2 domains of p85 is the critical step that activates PtdIns 3'-kinase during insulin stimulation...
  56. pmc Selective regulation of heme oxygenase-1 expression and function by insulin through IRS1/phosphoinositide 3-kinase/Akt-2 pathway
    Pedro Geraldes
    Research Division, Joslin Diabetes Center, Boston, MA 02215, USA
    J Biol Chem 283:34327-36. 2008
    ..Overexpression of an adenoviral vector of native IRS1, IRS2, and Akt dominant negative or small interfering RNA transfection of Akt1 and Akt2 targeted gene demonstrated ..
  57. ncbi Short-term in vivo inhibition of insulin receptor substrate-1 expression leads to insulin resistance, hyperinsulinemia, and increased adiposity
    Eliana P Araujo
    Department of Internal Medicine, State University of Campinas, Campinas, Sao Paolo, Brazil
    Endocrinology 146:1428-37. 2005
    ..Thus, acute inhibition of IRS-1 expression in rats leads to insulin resistance accompanied by activation of a growth-related pathway exclusively in white adipose tissue...
  58. ncbi A common mutation of the insulin receptor substrate-1 gene is a risk factor for coronary artery disease
    M G Baroni
    Istituto di II Clinica Medica, University of Rome La Sapienza, Policlinico Umberto I, Rome, Italy
    Arterioscler Thromb Vasc Biol 19:2975-80. 1999
    ..Besides the increased frequency of diabetes, carriers showed a more atherogenic lipid profile, suggesting a potential role of the IRS-1 gene in the pathogenesis of lipid abnormalities associated with CAD...
  59. pmc Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1
    X J Sun
    Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215
    Mol Cell Biol 13:7418-28. 1993
    ..These results extend the notion that IRS-1 is a multisite docking protein that engages various downstream regulatory elements during insulin signal transmission...
  60. ncbi Active Rho kinase (ROK-alpha ) associates with insulin receptor substrate-1 and inhibits insulin signaling in vascular smooth muscle cells
    Najma Begum
    Diabetes Research Laboratory, Winthrop University Hospital, Mineola, New York 11501, USA
    J Biol Chem 277:6214-22. 2002
    ....
  61. ncbi Phosphorylation of insulin receptor substrate-1 serine 307 correlates with JNK activity in atrophic skeletal muscle
    Thomas L Hilder
    Department of Pharmacology, University of North Carolina, Chapel Hill 27599 7365, USA
    FEBS Lett 553:63-7. 2003
    ..Moreover, we observed a corresponding reduction in Akt activity, providing biochemical evidence for the development of insulin resistance in atrophic skeletal muscle...
  62. ncbi Angiotensin-(1 7) stimulates the phosphorylation of JAK2, IRS-1 and Akt in rat heart in vivo: role of the AT1 and Mas receptors
    Jorge F Giani
    Instituto de Quimica y Fisicoquimica Biologicas, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires Consejo Nacional de Investigaciones Científicas y Tecnológicas, Buenos Aires, Argentina
    Am J Physiol Heart Circ Physiol 293:H1154-63. 2007
    ....
  63. ncbi Phosphorylation of the insulin receptor substrate IRS-1 by casein kinase II
    M J Tanasijevic
    Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts 02115
    J Biol Chem 268:18157-66. 1993
    ..Thus, casein kinase II-catalyzed phosphorylation of IRS-1 may be a component of the intracellular insulin signalling cascade...
  64. ncbi [Influence of chronic ethanol intake insulin sensitivity and IR, IRS-1, IRS-2 mRNA expression of liver in male rats]
    Shao Liang Zhou
    Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
    Wei Sheng Yan Jiu 35:294-6. 2006
    ..To investigate the effect of ethanol intake on the insulin sensitivity of hepatic tissue in male rats and explores its possible molecular mechanisms...
  65. ncbi The function of GRB2 in linking the insulin receptor to Ras signaling pathways
    E Y Skolnik
    Department of Pharmacology, New York University Medical Center, NY 10016
    Science 260:1953-5. 1993
    ....
  66. pmc Effect of testosterone on insulin stimulated IRS1 Ser phosphorylation in primary rat myotubes--a potential model for PCOS-related insulin resistance
    Michael C Allemand
    Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Mayo Clinic Graduate School of Medicine, Rochester, Minnesota, United States of America
    PLoS ONE 4:e4274. 2009
    ..The phosphorylation of Akt, mTOR, and S6K, downstream targets of the PI3-kinase-IRS-1 complex were also studied...
  67. ncbi Reduction of adiposity with prolonged growth hormone treatment in old obese rats: effects on glucose handling and early insulin signaling
    T Johansen
    Department of Pharmacological Research, Discovery, Novo Nordisk, DK 2760 Måløv, Denmark
    Growth Horm IGF Res 15:55-63. 2005
    ..To answer this question we assessed carbohydrate handling and tissue specific function of the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) during prolonged GH treatment of obese rats...
  68. pmc Low aerobic capacity and high-fat diet contribute to oxidative stress and IRS-1 degradation in the kidney
    E Matthew Morris
    Department of Internal Medicine, University of Missouri Columbia, Columbia, MO 65212, USA
    Am J Nephrol 30:112-9. 2009
    ..Thereby, we hypothesized intrinsically high aerobic fitness would protect against high-fat diet (HFD)-induced reactive oxygen species (ROS) and IRS-1 degradation...
  69. ncbi Altered subcellular distribution of IRS-1 and IRS-3 is associated with defective Akt activation and GLUT4 translocation in insulin-resistant old rat adipocytes
    Margarita Villar
    Area de Bioquímica, Facultad de Quimicas, Centro Regional de Investigaciones Biomédicas CRIB, Universidad de Castilla La Mancha, Avenida Camilo Jose Cela, 10 13071, Ciudad Real, Spain
    Biochim Biophys Acta 1763:197-206. 2006
    ..In addition, our data suggest that the mechanism of turning on/off insulin receptor-mediated signal is impaired with aging...
  70. pmc High-fat diet induces Ikkbeta and reduces insulin sensitivity in rats with low running capacity
    B T Bikman
    The Metabolic Institute for the Study of Diabetes and Obesity, East Carolina University, United States
    Int J Sports Med 30:631-5. 2009
    ..IRS-1 pSer (307) in the LCR rats increased on the HFD vs. chow. We conclude that differences in glucose tolerance between LCR and HCR rats are at least partly explained by differences in IKKbeta activity and pSer (307) levels...
  71. ncbi Insulin receptor substrates-1 and -2 are both depleted but via different mechanisms after down-regulation of glucose transport in rat adipocytes
    Frida Renstrom
    Department of Medicine, Umea University Hospital, SE 901 85 Umea, Sweden
    Endocrinology 146:3044-51. 2005
    ....
  72. ncbi Western diet modulates insulin signaling, c-Jun N-terminal kinase activity, and insulin receptor substrate-1ser307 phosphorylation in a tissue-specific fashion
    Patrícia Oliveira Prada
    Departamento de Clínica Médica da Universidade Estadual de Campinos, Campinas, Sao Paulo 13083 970, Brazil
    Endocrinology 146:1576-87. 2005
    ..The impairment of the insulin signaling in these tissues, but not in adipose tissue, may lead to increased adiposity and insulin resistance in the WD rats...
  73. doi Sex steroids influence glucose oxidation through modulation of insulin receptor expression and IRS-1 serine phosphorylation in target tissues of adult male rat
    Thirupathi Muthusamy
    Department of Endocrinology, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India
    Mol Cell Biochem 352:35-45. 2011
    ..It is concluded from the present study that sex steroid deficiency induces impaired glucose oxidation in insulin responsive tissues, which is mediated through reduced IR expression, and increased IRS-1 serine phosphorylation...
  74. doi [Bushen Huoxue Huayu Recipe up-regulates expression of insulin receptor substrate-1 and phosphorylation of tyrosine in adipose tissue in androgen sterilized rats]
    Xi Lian Li
    Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
    Zhong Xi Yi Jie He Xue Bao 6:621-5. 2008
    ....
  75. 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...
  76. ncbi Human, but not rat, IRS1 targets to the plasma membrane in both human and rat adipocytes
    Karin G Stenkula
    Department of Cell Biology, Linkoping University, SE58185 Linköping, Sweden
    Biochem Biophys Res Commun 363:840-5. 2007
    ..The activated insulin receptor phosphorylates insulin receptor substrate-1 (IRS1), which acts as a docking protein for downstream signal mediators...
  77. ncbi Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses
    Maja Jensen
    Receptor Systems Biology Laboratory, Hagedorn Research Institute, 2820 Gentofte, Denmark
    J Biol Chem 282:35179-86. 2007
    ..We show for the first time that it is possible to design insulin receptor ligand mimetics with metabolic equipotency but low mitogenicity...
  78. ncbi Human glycated albumin affects glucose metabolism in L6 skeletal muscle cells by impairing insulin-induced insulin receptor substrate (IRS) signaling through a protein kinase C alpha-mediated mechanism
    Claudia Miele
    Dipartimento di Biologia e Patologia Cellulare e Molecolare and Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Universita di Napoli Federico II, Via S Pansini, 5, 80131 Naples, Italy
    J Biol Chem 278:47376-87. 2003
    ..In summary, in L6 skeletal muscle cells, exposure to HGA leads to insulin resistance selectively in glucose metabolism with no effect on growth-related pathways regulated by the hormone...
  79. ncbi Depletion of mitochondrial DNA causes impaired glucose utilization and insulin resistance in L6 GLUT4myc myocytes
    Seung Y Park
    Department of Biochemistry, College of Medicine, Dongguk University, Kyungju 780 714, Korea
    J Biol Chem 280:9855-64. 2005
    ....
  80. ncbi Growth retardation alters the epigenetic characteristics of hepatic dual specificity phosphatase 5
    Qi Fu
    University of Utah School of Medicine, Department of Pediatrics, Division of Neonatology, P O Box 581289, Salt Lake City, UT 84158, USA
    FASEB J 20:2127-9. 2006
    ....
  81. ncbi Insulin receptor substrate-1 is present in hepatocyte nuclei from intact rats
    Joan M Boylan
    Division of Pediatric Endocrinology and Metabolism, Rhode Island Hospital and Brown University, Providence, Rhode Island 02903, USA
    Endocrinology 143:4178-83. 2002
    ..Our results indicate that insulin signaling, which terminates in an array of nuclear events, may originate at the immediate postreceptor level with IRS-1 activation within the nucleus of normal hepatocytes...
  82. ncbi Identification of a NPXY motif in growth factor receptor-bound protein 14 (Grb14) and its interaction with the phosphotyrosine-binding (PTB) domain of IRS-1
    Raju V S Rajala
    Department of Cell Biology, University of Oklahoma Health Sciences Center, and Dean A McGee Eye Institute, Oklahoma City, Oklahoma 73104, USA
    Biochemistry 44:7929-35. 2005
    ..This is the first report describing the presence of the NPXY motif in Grb14 and binding of the PTB domain of IRS-1 in a phosphorylation-independent manner...
  83. pmc IRS1 regulation by Wnt/beta-catenin signaling and varied contribution of IRS1 to the neoplastic phenotype
    Guido T Bommer
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 285:1928-38. 2010
    ..Based on the results of microarray-based gene expression profiling we found the insulin receptor substrate 1 (IRS1) gene as one of the most highly up-regulated genes upon ectopic expression of a mutant, constitutively active form ..
  84. ncbi Diversification of cardiac insulin signaling involves the p85 alpha/beta subunits of phosphatidylinositol 3-kinase
    A Kessler
    Laboratory of Molecular Cardiology, Diabetes Research Institute, D 40225 Dusseldorf, Germany
    Am J Physiol Endocrinol Metab 280:E65-74. 2001
    ..Furthermore, multiple defects of PI 3-kinase activation, involving both the p85 alpha and the p85 beta adaptor subunits, may contribute to cardiac insulin resistance...
  85. ncbi [Effects of aging on the expressions of insulin receptor substrate-1, phosphate protein kinase B in rat liver and muscle]
    Shuang Wang
    Department of Endocrinology, West China Hospital, Sichuan University, Chengdu 610041, China
    Sichuan Da Xue Xue Bao Yi Xue Ban 40:426-9. 2009
    ..To investigate the effects of aging on the levels of free fatty acid (FFA), lipid profile, the expression of IRS-1 and its downstream signal Akt phosphorylation, so to explore the mechanisms of aging-associated glucose tolerance impairment...
  86. ncbi Dihydrotestosterone inhibits insulin-stimulated cyclin D2 messenger ribonucleic acid expression in rat ovarian granulosa cells by reducing the phosphorylation of insulin receptor substrate-1
    Pradeep P Kayampilly
    Departments of Obstetrics and Gynecology and Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Endocrinology 147:464-71. 2006
    ....
  87. doi Chronic-intermittent cold stress in rats induces selective ovarian insulin resistance
    Mauricio Dorfman
    Laboratory of Neurobiochemistry, Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago 838 0492, Chile
    Biol Reprod 80:264-71. 2009
    ..The levels of mRNA and protein for IRS1 and SLC2A4 (also known as GLUT4), molecules involved in insulin signaling, decreased significantly in the ovaries ..
  88. ncbi Prolactin stimulates proliferation of the glucose-dependent beta-cell line INS-1 via different IRS-proteins
    Sigrun R Hugl
    Department of Internal Medicine, University of Ulm, Ulm, Germany
    JOP 8:739-52. 2007
    ..Prolactin is one of the most potent growth stimulating growth hormones of pancreatic beta cells...
  89. doi Effect of fetal dexamethasone exposure on the development of adult insulin sensitivity in a rat model
    KAREN O'BRIEN
    Women and Infants Hospital of Rhode Island, Providence, RI, USA
    J Matern Fetal Neonatal Med 21:623-8. 2008
    ..Additionally, the study investigated whether a differential effect exists in male and female rodent offspring, such that females demonstrate decreased binding of p85 to IRS-1 after exposure to dexamethasone in utero...
  90. ncbi Reduced CTL response and increased viral burden in substance P receptor-deficient mice infected with murine gamma-herpesvirus 68
    Sherine F Elsawa
    Department of Biology, University of North Carolina, Charlotte, NC 28223, USA
    J Immunol 170:2605-12. 2003
    ..These studies demonstrate that genetic elimination of substance P receptors in mice results in an increased gamma-herpesvirus burden and an altered host response...
  91. ncbi Purification and partial sequence analysis of pp185, the major cellular substrate of the insulin receptor tyrosine kinase
    P L Rothenberg
    Research Division, Joslin Diabetes Center, Boston, Massachusetts
    J Biol Chem 266:8302-11. 1991
    Insulin stimulates the tyrosine phosphorylation of a 185-kDa putative cytosolic substrate protein (pp185) in diverse cell types...
  92. pmc Interaction between serine phosphorylated IRS-1 and beta1-integrin affects the stability of neuronal processes
    Jin Ying Wang
    Center for Neurovirology, Department of Neuroscience, School of Medicine, Temple University, Philadelphia, Pennsylvania 19122, USA
    J Neurosci Res 85:2360-73. 2007
    ..IGF-I counteracts TNFalpha-mediated accumulation of pS-IRS-1-beta1-integrin complexes supporting the stability of neuronal processes...

Research Grants13

  1. MECHANISMS OF PROTEIN ACCUMULATION IN RENAL HYPERTROPHY
    Harold Franch; Fiscal Year: 2002
    ..It should also lay the ground work for further investigations into the mechanisms behind renal hypertrophy. ..
  2. Mechanism of Protein Accumulation in Renal Hypertrophy
    Harold A Franch; Fiscal Year: 2010
    ..This proposal studies how this same process may be important for destroying proteins damaged by diabetes that contribute to kidney disease. ..
  3. Light Activation of Retinal Insulin Receptor Signaling
    RAJU RAJALA; Fiscal Year: 2009
    ..The biological implications extend to the cause and treatment of a number of retinal degenerative diseases. ..
  4. Light Activation of Retinal Insulin Receptor Signaling
    RAJU RAJALA; Fiscal Year: 2007
    ..The biological implications extend to the cause and treatment of a number of retinal degenerative diseases. ..
  5. Impaired insulin signaling: Mechanisms of and reversibility in two rodent models
    BEN YASPELKIS; Fiscal Year: 2007
    ....
  6. Is Tissue ACE Required for Diabetic Renal Damage?
    Harold Franch; Fiscal Year: 2005
    ..We believe that this approach will not only critically test our hypothesis, but will also lay the ground work for future studies into the role of ACE in the diabetic kidney. ..
  7. INSULIN RECEPTOR SIGNALING IN THE RETINA
    RAJU RAJALA; Fiscal Year: 2002
    ..The biological implication extends to the cause and treatment of a number of retinal degenerative diseases. ..
  8. Light Activation of Retinal Insulin Receptor Signaling
    RAJU VS RAJALA; Fiscal Year: 2010
    ..Studies proposed in this grant application would help to understand the functional roles of IR and IGF-1R in photoreceptor structure, function and survival. ..