Genomes and Genes
Gene Symbol: Irs1
Description: insulin receptor substrate 1
Alias: IRS1IRM, IRS-1, pp185
- Bradykinin augments insulin-stimulated glucose transport in rat adipocytes via endothelial nitric oxide synthase-mediated inhibition of Jun NH2-terminal kinaseKristin 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...
- Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive declineKonrad Talbot
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 3403, USA
J Clin Invest 122:1316-38. 2012....
- Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscleChunli 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...
- Acute physical exercise reverses S-nitrosation of the insulin receptor, insulin receptor substrate 1 and protein kinase B/Akt in diet-induced obese Wistar ratsJose 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...
- Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloadingReiko 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...
- Endotoxin mediated-iNOS induction causes insulin resistance via ONOO⁻ induced tyrosine nitration of IRS-1 in skeletal muscleGenevieve 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...
- Glomerular-specific protein kinase C-β-induced insulin receptor substrate-1 dysfunction and insulin resistance in rat models of diabetes and obesityAkira 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 ..
- 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) pathwaysSoojeong 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 ..
- Aspirin inhibits serine phosphorylation of IRS-1 in muscle and adipose tissue of septic ratsGuilherme 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...
- Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction proteinX 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...
- Oxidant stress-induced loss of IRS-1 and IRS-2 proteins in rat skeletal muscle: role of p38 MAPKTara 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....
- Role of insulin receptor substrate-1 serine 307 phosphorylation and adiponectin in adipose tissue insulin resistance in late pregnancyJulio 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...
- Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistanceLeila 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...
- Nuclear matrix association of insulin receptor and IRS-1 by insulin in osteoblast-like UMR-106 cellsKi 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...
- The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signallingE 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...
- Silencing of insulin receptor substrate-1 increases cell death in retinal Müller cellsRobert 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...
- 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-cellsFrancesco 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...
- Mechanisms of reactive oxygen species-dependent downregulation of insulin receptor substrate-1 by angiotensin IIYoshihiro 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)...
- Loss of inhibitory insulin receptor substrate-1 phosphorylation is an early event in mammalian target of rapamycin-dependent endometrial hyperplasia and carcinomaAdrienne 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....
- Regulation of IRS-1/SHP2 interaction and AKT phosphorylation in animal models of insulin resistanceMaria Helena M Lima
Department of Internal Medicine, State University of Campinas, SP, Brazil
Endocrine 18:1-12. 2002....
- High-fat feeding increases insulin receptor and IRS-1 coimmunoprecipitation with SOCS-3, IKKalpha/beta phosphorylation and decreases PI-3 kinase activity in muscleBen 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....
- 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 ratsMichael 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...
- O-linked N-acetylglucosamine modification of insulin receptor substrate-1 occurs in close proximity to multiple SH2 domain binding motifsAmanda 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...
- Association studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onsetEleftheria Zeggini
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
Diabetes 53:3319-22. 2004The gene encoding insulin receptor substrate-1 (IRS1) represents a strong biological candidate for a contributory role in type 2 diabetes susceptibility...
- Insulin receptor substrate-1/SHP-2 interaction, a phenotype-dependent switching machinery of insulin-like growth factor-I signaling in vascular smooth muscle cellsKen 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....
- A novel regulation of IRS1 (insulin receptor substrate-1) expression following short term insulin administrationAntonio 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...
- Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin actionVincent 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...
- Reversal of diet-induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS-1 serine phosphorylationEduardo 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...
- Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistanceR 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...
- Regulation of insulin receptor substrate 1 pleckstrin homology domain by protein kinase C: role of serine 24 phosphorylationRanmali 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 ..
- 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....
- Functional studies of Akt isoform specificity in skeletal muscle in vivo; maintained insulin sensitivity despite reduced insulin receptor substrate-1 expressionMark 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...
- Adrenaline potentiates insulin-stimulated PKB activation in the rat fast-twitch epitrochlearis muscle without affecting IRS-1-associated PI 3-kinase activityJørgen 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...
- Phosphorylation of Ser357 of rat insulin receptor substrate-1 mediates adverse effects of protein kinase C-delta on insulin action in skeletal muscle cellsRizwana 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...
- 53BP2S, interacting with insulin receptor substrates, modulates insulin signalingFumihiko 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...
- 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 modelTokio 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...
- Antidepressants induce cellular insulin resistance by activation of IRS-1 kinasesYechiel 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...
- Aldosterone suppresses insulin signaling via the downregulation of insulin receptor substrate-1 in vascular smooth muscle cellsHirofumi Hitomi
Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kita gun, Japan
Hypertension 50:750-5. 2007....
- Common inhibitory serine sites phosphorylated by IRS-1 kinases, triggered by insulin and inducers of insulin resistanceAvia 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...
- 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 transportC 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...
- A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscleErin 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....
- beta-arrestin-1 competitively inhibits insulin-induced ubiquitination and degradation of insulin receptor substrate 1Isao 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....
- Regulation of insulin receptor substrate-1 in the liver, skeletal muscle and adipose tissue of rats throughout pregnancyC Gonzalez
Department of Functional Biology, Physiology Area, University of Oviedo, c Julian Claveria s n, 33006 Oviedo, Spain
Gynecol Endocrinol 17:187-97. 2003....
- TGF-beta 1 modulation of IGF-I signaling pathway in rat thyroid epithelial cellsGabriella 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...
- A novel T608R missense mutation in insulin receptor substrate-1 identified in a subject with type 2 diabetes impairs metabolic insulin signalingDiana 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 ..
- 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-1Klaus 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...
- Acidosis impairs insulin receptor substrate-1-associated phosphoinositide 3-kinase signaling in muscle cells: consequences on proteolysisHarold 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...
- 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 cellsLuciano 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...
- In vivo phosphorylation of insulin receptor substrate 1 at serine 789 by a novel serine kinase in insulin-resistant rodentsLi 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...
- SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptinChaojun 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...
- Insulin signaling through insulin receptor substrate 1 and 2 in normal liver developmentLeila 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...
- Insulin resistance: interactions between obesity and a common variant of insulin receptor substrate-1J 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...
- Serine 332 phosphorylation of insulin receptor substrate-1 by glycogen synthase kinase-3 attenuates insulin signalingZiva 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...
- 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 proteinB 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....
- Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulationJ 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...
- Selective regulation of heme oxygenase-1 expression and function by insulin through IRS1/phosphoinositide 3-kinase/Akt-2 pathwayPedro 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 ..
- Short-term in vivo inhibition of insulin receptor substrate-1 expression leads to insulin resistance, hyperinsulinemia, and increased adiposityEliana 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...
- A common mutation of the insulin receptor substrate-1 gene is a risk factor for coronary artery diseaseM 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...
- Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1X 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...
- Active Rho kinase (ROK-alpha ) associates with insulin receptor substrate-1 and inhibits insulin signaling in vascular smooth muscle cellsNajma Begum
Diabetes Research Laboratory, Winthrop University Hospital, Mineola, New York 11501, USA
J Biol Chem 277:6214-22. 2002....
- Phosphorylation of insulin receptor substrate-1 serine 307 correlates with JNK activity in atrophic skeletal muscleThomas 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...
- Angiotensin-(1 7) stimulates the phosphorylation of JAK2, IRS-1 and Akt in rat heart in vivo: role of the AT1 and Mas receptorsJorge 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....
- Phosphorylation of the insulin receptor substrate IRS-1 by casein kinase IIM 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...
- [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...
- The function of GRB2 in linking the insulin receptor to Ras signaling pathwaysE Y Skolnik
Department of Pharmacology, New York University Medical Center, NY 10016
Science 260:1953-5. 1993....
- Effect of testosterone on insulin stimulated IRS1 Ser phosphorylation in primary rat myotubes--a potential model for PCOS-related insulin resistanceMichael 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...
- Reduction of adiposity with prolonged growth hormone treatment in old obese rats: effects on glucose handling and early insulin signalingT 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...
- Low aerobic capacity and high-fat diet contribute to oxidative stress and IRS-1 degradation in the kidneyE 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...
- Altered subcellular distribution of IRS-1 and IRS-3 is associated with defective Akt activation and GLUT4 translocation in insulin-resistant old rat adipocytesMargarita 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...
- High-fat diet induces Ikkbeta and reduces insulin sensitivity in rats with low running capacityB 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...
- Insulin receptor substrates-1 and -2 are both depleted but via different mechanisms after down-regulation of glucose transport in rat adipocytesFrida Renstrom
Department of Medicine, Umea University Hospital, SE 901 85 Umea, Sweden
Endocrinology 146:3044-51. 2005....
- Western diet modulates insulin signaling, c-Jun N-terminal kinase activity, and insulin receptor substrate-1ser307 phosphorylation in a tissue-specific fashionPatrícia 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...
- Sex steroids influence glucose oxidation through modulation of insulin receptor expression and IRS-1 serine phosphorylation in target tissues of adult male ratThirupathi 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...
- [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....
- Modulation of IR/PTP1B interaction and downstream signaling in insulin sensitive tissues of MSG-ratsAparecida 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...
- Human, but not rat, IRS1 targets to the plasma membrane in both human and rat adipocytesKarin 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...
- Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responsesMaja 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...
- 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 mechanismClaudia 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...
- Depletion of mitochondrial DNA causes impaired glucose utilization and insulin resistance in L6 GLUT4myc myocytesSeung Y Park
Department of Biochemistry, College of Medicine, Dongguk University, Kyungju 780 714, Korea
J Biol Chem 280:9855-64. 2005....
- Growth retardation alters the epigenetic characteristics of hepatic dual specificity phosphatase 5Qi 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....
- Insulin receptor substrate-1 is present in hepatocyte nuclei from intact ratsJoan 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...
- Identification of a NPXY motif in growth factor receptor-bound protein 14 (Grb14) and its interaction with the phosphotyrosine-binding (PTB) domain of IRS-1Raju 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...
- IRS1 regulation by Wnt/beta-catenin signaling and varied contribution of IRS1 to the neoplastic phenotypeGuido 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 ..
- Diversification of cardiac insulin signaling involves the p85 alpha/beta subunits of phosphatidylinositol 3-kinaseA 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...
- [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...
- Dihydrotestosterone inhibits insulin-stimulated cyclin D2 messenger ribonucleic acid expression in rat ovarian granulosa cells by reducing the phosphorylation of insulin receptor substrate-1Pradeep 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....
- Chronic-intermittent cold stress in rats induces selective ovarian insulin resistanceMauricio 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 ..
- Prolactin stimulates proliferation of the glucose-dependent beta-cell line INS-1 via different IRS-proteinsSigrun 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...
- Effect of fetal dexamethasone exposure on the development of adult insulin sensitivity in a rat modelKAREN 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...
- Reduced CTL response and increased viral burden in substance P receptor-deficient mice infected with murine gamma-herpesvirus 68Sherine 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...
- Purification and partial sequence analysis of pp185, the major cellular substrate of the insulin receptor tyrosine kinaseP L Rothenberg
Research Division, Joslin Diabetes Center, Boston, Massachusetts
J Biol Chem 266:8302-11. 1991Insulin stimulates the tyrosine phosphorylation of a 185-kDa putative cytosolic substrate protein (pp185) in diverse cell types...
- Interaction between serine phosphorylated IRS-1 and beta1-integrin affects the stability of neuronal processesJin 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...
- MECHANISMS OF PROTEIN ACCUMULATION IN RENAL HYPERTROPHYHarold Franch; Fiscal Year: 2002..It should also lay the ground work for further investigations into the mechanisms behind renal hypertrophy. ..
- Mechanism of Protein Accumulation in Renal HypertrophyHarold 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. ..
- Light Activation of Retinal Insulin Receptor SignalingRAJU RAJALA; Fiscal Year: 2009..The biological implications extend to the cause and treatment of a number of retinal degenerative diseases. ..
- Light Activation of Retinal Insulin Receptor SignalingRAJU RAJALA; Fiscal Year: 2007..The biological implications extend to the cause and treatment of a number of retinal degenerative diseases. ..
- Impaired insulin signaling: Mechanisms of and reversibility in two rodent modelsBEN YASPELKIS; Fiscal Year: 2007....
- 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. ..
- INSULIN RECEPTOR SIGNALING IN THE RETINARAJU RAJALA; Fiscal Year: 2002..The biological implication extends to the cause and treatment of a number of retinal degenerative diseases. ..
- Light Activation of Retinal Insulin Receptor SignalingRAJU 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. ..