Research Topics
Genomes and Genes | Morris WhiteSummaryAffiliation: Harvard University Country: USA Publications
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Publications
Phosphorylation of Irs1 at SER-522 inhibits insulin signalingJodel Giraud
Howard Hughes Medical Institute, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Endocrinol 21:2294-302. 2007..Together, these results suggest the phosphatidylinositol 3-kinase-->Akt cascade can inhibit insulin signaling through the phosphorylation of S522(Irs1)...
Human IL6 enhances leptin action in miceM Sadagurski
Howard Hughes Medical Institute, Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, Karp Family Research Laboratories, Rm 4210, 300 Longwood Avenue, Boston, MA 02115, USA
Diabetologia 53:525-35. 2010..Many reports show that circulating IL6 correlates with obesity and contributes to insulin resistance; however, IL6 can promote energy expenditure that improves glucose homeostasis...
Deletion of Irs2 causes reduced kidney size in mice: role for inhibition of GSK3beta?Rosemarie M Carew
UCD Diabetes Research Centre, UCD Conway Institute, School of Medicine and Medical Science, University College Dublin, Belfield Dublin 4, Ireland
BMC Dev Biol 10:73. 2010..Defects in neuronal proliferation, pituitary development and photoreceptor cell survival manifest in Irs2-/- mice. We identify retarded renal growth in male and female Irs2-/- mice, independent of diabetes...
Regulating insulin signaling and beta-cell function through IRS proteinsMorris F White
Howard Hughes Medical Institute, Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, Karp Family Research Laboratories, Room 4210, 300 Longwood Avenue, Boston, MA 02115, USA
Can J Physiol Pharmacol 84:725-37. 2006..Understanding the molecular basis of insulin resistance can prevent these disorders and their inevitable progression to type 2 diabetes...
Metformin and insulin meet in a most atypical wayMorris F White
Howard Hughes Medical Institute, Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
Cell Metab 9:485-7. 2009....
Molecular mechanism(s) of burn-induced insulin resistance in murine skeletal muscle: role of IRS phosphorylationQin Zhang
Department of Surgery, Massachusetts General Hospital and Shriners Hospital for Children, Harvard Medical School, Boston, MA 02114, USA
Life Sci 77:3068-77. 2005....
Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetesXueying Lin
Howard Hughes Medical Institute Children s Hospital, Division of Endocrinology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Clin Invest 114:908-16. 2004..Thus, Irs2 signaling promotes regeneration of adult beta cells and central control of nutrient homeostasis, which can prevent obesity and diabetes in mice...
Exendin-4 uses Irs2 signaling to mediate pancreatic beta cell growth and functionSunmin Park
Howard Hughes Medical Institute, Division of Endocrinology, Department of Medicine, Children s Hospital Boston, MA 02215, USA
J Biol Chem 281:1159-68. 2006....
Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetesAnita M Hennige
Howard Hughes Medical Institute, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
J Clin Invest 112:1521-32. 2003..Thus, pharmacological approaches that promote Irs2 expression in beta cells, especially specific cAMP agonists, could be rational treatments for beta cell failure and diabetes...
Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulationXiaocheng C Dong
Howard Hughes Medical Institute, Division of Endocrinology, Children s Hospital Boston, Karp Family Research Laboratories, 300 Longwood Avenue, Harvard Medical School, Boston, MA 02115, USA
Cell Metab 8:65-76. 2008....
Pdx1 restores beta cell function in Irs2 knockout miceJake A Kushner
Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Clin Invest 109:1193-201. 2002..Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY...
Insulin resistance in thermally-injured rats is associated with post-receptor alterations in skeletal muscle, liver and adipose tissueEdward A Carter
Department of Pediatrics, Shriners Hospital for Children, 16 Blossom Street, Boston, MA 02114, USA
Int J Mol Med 14:653-8. 2004....
IRS proteins and the common path to diabetesMorris F White
Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Am J Physiol Endocrinol Metab 283:E413-22. 2002....
Insulin receptor substrate 2 is essential for maturation and survival of photoreceptor cellsXianjin Yi
Howard Hughes Medical Institute, Children s Hospital Boston, Boston, Massachusetts 02115, USA
J Neurosci 25:1240-8. 2005....
Islet-sparing effects of protein tyrosine phosphatase-1b deficiency delays onset of diabetes in IRS2 knockout miceJake A Kushner
Howard Hughes Medical Institute, Joslin Diabetes Center, and Division of Endocrinology, Children s Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA
Diabetes 53:61-6. 2004..Our studies demonstrate a novel role for Ptp1b in regulating beta-cell homeostasis and indicate that Ptp1b deficiency can partially compensate for lack of Irs2...
Insulin signaling in health and diseaseMorris 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. This knowledge will lead to rational strategies that prevent or cure diabetes...
Alterations in growth and apoptosis of insulin receptor substrate-1-deficient beta-cellsAnita M Hennige
Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
Am J Physiol Endocrinol Metab 289:E337-46. 2005....
Targeted disruption of ROCK1 causes insulin resistance in vivoDae Ho Lee
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 284:11776-80. 2009..Thus, our results identify ROCK1 as a novel regulator of glucose homeostasis and insulin sensitivity in vivo, which could lead to new treatment approaches for obesity and type 2 diabetes...
Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parentsKatsutaro Morino
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536 8012, USA
J Clin Invest 115:3587-93. 2005....
Muscle-specific IRS-1 Ser->Ala transgenic mice are protected from fat-induced insulin resistance in skeletal muscleKatsutaro Morino
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA
Diabetes 57:2644-51. 2008..In this study, we examine the role of serine phosphorylation of insulin receptor substrate (IRS)-1 in mediating fat-induced insulin resistance in skeletal muscle in vivo...
Phosphatase and tensin homolog regulation of islet growth and glucose homeostasisJake A Kushner
Division of Endocrinology, Children s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 280:39388-93. 2005..Thus, steps to enhance phosphatidylinositol 3-kinase signaling can promote beta-cell growth, function, and survival without the Irs2 branch of the insulin/insulin-like growth factor signaling cascade...
Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growthXiaocheng Dong
Howard Hughes Medical Institute, Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
J Clin Invest 116:101-14. 2006..Thus, signals delivered by Irs1 or Irs2 regulate hepatic gene expression that coordinates glucose homeostasis and systemic growth...
Brain IRS2 signaling coordinates life span and nutrient homeostasisAkiko Taguchi
Howard Hughes Medical Institute, Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
Science 317:369-72. 2007..Thus, less Irs2 signaling in aging brains can promote healthy metabolism, attenuate meal-induced oxidative stress, and extend the life span of overweight and insulin-resistant mice...
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...
SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2Liangyou Rui
Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 277:42394-8. 2002..Thus, SOCS-mediated degradation of IRS proteins, presumably via the elongin BC ubiquitin-ligase, might be a general mechanism of inflammation-induced insulin resistance, providing a target for therapy...
Insulin signaling after exercise in insulin receptor substrate-2-deficient miceKirsten F Howlett
Research Division, Joslin Diabetes Center and Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA
Diabetes 51:479-83. 2002..IRS-2 signaling can partially account for the increase in insulin-stimulated phosphotyrosine-associated PI 3-kinase activity after exercise...
Role of insulin receptor substrates and protein kinase C-zeta in vascular permeability factor/vascular endothelial growth factor expression in pancreatic cancer cellsMatthias Neid
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 279:3941-8. 2004..Our data also suggest that IRS proteins, which are known to play crucial roles in IGF-1R signaling, are also important mediators for tumor angiogenesis...
Cyclins D2 and D1 are essential for postnatal pancreatic beta-cell growthJake A Kushner
Division of Endocrinology, Children s Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA
Mol Cell Biol 25:3752-62. 2005..Thus, cyclins D2 and D1 were essential for beta-cell expansion in adult mice. Strategies to tightly regulate D-type cyclin activity in beta cells could prevent or cure diabetes...
Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylationMarkus Schubert
Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Neurosci 23:7084-92. 2003..Thus, dysregulation of the Irs2 branch of the insulin-Igf-signaling cascade reveals a molecular link between diabetes and neurodegenerative disease...
c-Jun N-terminal kinase (JNK) mediates feedback inhibition of the insulin signaling cascadeYong Hee Lee
Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 278:2896-902. 2003..These results support the hypothesis that JNK is a negative feedback regulator of insulin action by phosphorylating Ser(307) in Irs1...
Constitutive activation of insulin receptor substrate 1 is a frequent event in human tumors: therapeutic implicationsQing Chang
Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
Cancer Res 62:6035-8. 2002..These studies suggest that constitutive IRS-1 activation is a common phenomenon in tumors and that activated IRS-1 may present an attractive therapeutic target...
Nutrient-dependent and insulin-stimulated phosphorylation of insulin receptor substrate-1 on serine 302 correlates with increased insulin signalingJodel Giraud
Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 279:3447-54. 2004..Replacing Ser(302) with alanine reduced insulin/IGF-I-stimulated DNA synthesis. We conclude that Ser(302) phosphorylation integrates nutrient availability with insulin/IGF-I signaling to promote mitogenesis and cell growth...
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...
Foxo1 integrates insulin signaling with mitochondrial function in the liverZhiyong Cheng
Harvard Medical School, Boston, Massachusetts, USA
Nat Med 15:1307-11. 2009..Thus, Foxo1 integrates insulin signaling with mitochondrial function, and inhibition of Foxo1 can improve hepatic metabolism during insulin resistance and the metabolic syndrome...
Involvement of insulin receptor substrate 2 in mammary tumor metastasisJulie A Nagle
Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Mol Cell Biol 24:9726-35. 2004..In contrast, IRS-1(-/-) tumor cells, which express only IRS-2, were highly invasive and were resistant to apoptotic stimuli. Collectively, our findings reveal an important contribution of IRS-2 to breast cancer metastasis...
The reciprocal stability of FOXO1 and IRS2 creates a regulatory circuit that controls insulin signalingShaodong Guo
Howard Hughes Medical Institute, Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, Karp Family Research Laboratories, Room 04210, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
Mol Endocrinol 20:3389-99. 2006..The dynamic relation between Irs2 and FoxO expression, compared with the subordinate role of Irs1, can explain the dominant role of Irs2 in metabolic regulation...
The Irs1 branch of the insulin signaling cascade plays a dominant role in hepatic nutrient homeostasisShaodong Guo
Howard Hughes Medical Institute, Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, Karp Family Research Laboratories, Boston, MA 02115, USA
Mol Cell Biol 29:5070-83. 2009..Moreover, LKO1 mice -- but not LKO2 mice -- that were fed a high-fat diet developed postprandial hyperglycemia. We conclude that Irs1 is the principal mediator of hepatic insulin action that maintains glucose homeostasis...
Insulin-like growth factor 2 and the insulin receptor, but not insulin, regulate fetal hepatic glycogen synthesisLi Liang
Department of Medicine Endocrine Division, Children s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
Endocrinology 151:741-7. 2010....
Irs1 serine 307 promotes insulin sensitivity in miceKYLE D COPPS
Children s Hospital Boston, Harvard Medical School, MA 02115, USA
Cell Metab 11:84-92. 2010..Thus, contrary to the results of cell-based experiments, Ser307 in mice is a positive regulatory site that moderates the severity of insulin resistance by maintaining proximal insulin signaling...
Stat6 and IRS-2 cooperate in interleukin 4 (IL-4)-induced proliferation and differentiation but are dispensable for IL-4-dependent rescue from apoptosisAndrea L Wurster
Department of Immunology and Infectious Diseases, Harvard School of Public Health. Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell Biol 22:117-26. 2002....
Signaling pathways: the benefits of good communicationTracey L Fisher
Howard Hughes Medical Institute, Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
Curr Biol 14:R1005-7. 2004..This crosstalk reveals how hyperactivated mTOR may suppress metastasis locally, while causing systemic insulin resistance that can progress to diabetes...
Overexpression or ablation of JNK in skeletal muscle has no effect on glycogen synthase activityNobuharu Fujii
Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA
Am J Physiol Cell Physiol 287:C200-8. 2004..JNK activation is unlikely to be the major mechanism by which contractile activity increases glycogen synthase activity in skeletal muscle...
Insulin-like signaling, nutrient homeostasis, and life spanAkiko 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...
Insulin receptor substrates Irs1 and Irs2 coordinate skeletal muscle growth and metabolism via the Akt and AMPK pathwaysYun Chau Long
Howard Hughes Medical Institute, Division of Endocrinology, Children s Hospital Boston, Center for Life Sciences, CLS 16020, 3 Blackfan Circle, Boston, MA 02115, USA
Mol Cell Biol 31:430-41. 2011..Thus, insulin-like signaling via Irs1/2 is essential to terminate skeletal muscle catabolic/fasting pathways in the presence of adequate nutrition...
Insulin receptor substrate-2 in beta-cells decreases diabetes in nonobese diabetic miceLisa D Norquay
Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
Endocrinology 150:4531-40. 2009..In conclusion, increased Irs2 attenuated the progression of beta-cell destruction, promoted beta-cell mitogenesis, and reduced diabetes incidence in NOD(Irs2) mice...
Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intoleranceChaojun Duan
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109 0622, USA
Mol Cell Biol 24:7435-43. 2004..Our data suggest that SH2-B is a physiological enhancer of insulin receptor activation and is required for maintaining normal insulin sensitivity and glucose homeostasis during aging...
Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic miceTohru Uchida
Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
Nat Med 11:175-82. 2005..Thus, p27(Kip1) contributes to beta-cell failure during the development of type 2 diabetes in Irs2(-/-) and Lepr(-/-) mice and represents a potential new target for the treatment of this condition...
Plasma insulin levels predict the development of atherosclerosis when IRS2 deficiency is combined with severe hypercholesterolemia in apolipoprotein E-null miceHerminia Gonzalez Navarro
Vascular Biology Laboratory, Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia IBV CSIC, Valencia, Spain
Front Biosci 12:2291-8. 2007..Future studies are necessary to determine whether IRS2 dysfunction may promote atherosclerosis in normoglycemic, pre-diabetic patients with clinical manifestations of hyperinsulinemia and insulin resistance...
Specificity of interleukin-2 receptor gamma chain superfamily cytokines is mediated by insulin receptor substrate-dependent pathwayHui Xiao
Department of Pharmacology and Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 4965, USA
J Biol Chem 277:8091-8. 2002..These data suggest that IRS-dependent signaling pathways work by recruiting different signaling molecules to determine specificity of IL-2R gamma superfamily cytokines...
IRS-2 mediates the antiapoptotic effect of insulin in neonatal hepatocytesAngela M Valverde
Instituto de Bioquímica Departamento de Bioquímica y Biología Molecular II, Centro Mixto CSIC UCM, Facultad de Farmacia, Universidad Complutense, Madrid, Spain
Hepatology 40:1285-94. 2004..Epidermal growth factor, via PIP3/Akt/Foxo1 phosphorylation, was able to rescue IRS-2(-/-) hepatocytes from serum withdrawal-induced apoptosis, modulating pro- and anti-apoptotic gene expression and downregulating caspase-3 activity...
Mammalian target of rapamycin regulates IRS-1 serine 307 phosphorylationChristian J Carlson
Insulin Signaling, Metabolic Diseases Division, Global Pharmaceutical Research Division, Abbott Laboratories, Abbott Park, IL 60064, USA
Biochem Biophys Res Commun 316:533-9. 2004..Finally, we demonstrated that serine 307 phosphorylated IRS-1 is detected primarily in the cytosolic fraction...
Insulin receptor substrate proteins and diabetesYong Hee Lee
Institute for Tumor Research, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea
Arch Pharm Res 27:361-70. 2004..Understanding the regulation and signaling by IRS1 and IRS2 in cell growth, metabolism and survival will reveal new strategies to prevent or cure diabetes and other metabolic diseases...
Attenuation of accumulation of neointimal lipid by pioglitazone in mice genetically deficient in insulin receptor substrate-2 and apolipoprotein EMaria H Clough
Department of Pathology, 89 Beaumont Avenue, College of Medicine, University of Vermont, Burlington, VT 05405, USA
J Histochem Cytochem 53:603-10. 2005..018. Accordingly, genetically induced intensification of insulin resistance increases atheroma formation. Furthermore, attenuation of insulin resistance by treatment with pioglitazone decreases accumulation of lipid in the neointima...
Essential role of protein kinase C zeta in the impairment of insulin-induced glucose transport in IRS-2-deficient brown adipocytesMonica Arribas
Departamento de Bioquímica y Biología Molecular Instituto de Bioquímica, Centro Mixto CSIC UCM, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
FEBS Lett 536:161-6. 2003..Our results support the essential role played by PKC zeta in the insulin resistance and impaired glucose uptake observed in IRS-2-deficient brown adipocytes...
The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growthTadahiro 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..We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts...
Analysis of compensatory beta-cell response in mice with combined mutations of Insr and Irs2Jane J Kim
Deparment of Pediatrics, University of California, San Diego, California, USA
Am J Physiol Endocrinol Metab 292:E1694-701. 2007..The eventual failure of compensatory insulin secretion suggests that a comprehensive treatment of beta-cell dysfunction in type 2 diabetes should positively affect both aspects of beta-cell physiology...
Insulin receptor substrate 1 (IRS-1) plays a unique role in normal epidermal physiologyMarianna Sadagurski
Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
J Cell Physiol 213:519-27. 2007..Furthermore, we suggest that IRS-1 and IRS-2 have distinct roles in skin physiology...
Molecular mechanisms of insulin resistance in IRS-2-deficient hepatocytesAngela M Valverde
Instituto de Bioquímica Departamento de Bioquímica y Biología Molecular II, Centro Mixto CSIC UCM, Facultad de Farmacia, Universidad Complutense, Madrid, Spain
Diabetes 52:2239-48. 2003..Suppression of gluconeogenic gene expression in IRS-2-deficient primary hepatocytes was also restored by infection with dominant negative Delta 256Foxo1...
The repression of IRS2 gene by ATF3, a stress-inducible gene, contributes to pancreatic beta-cell apoptosisDan Li
Department of Molecular and Cellular Biochemistry, Center for Molecular Neurobiology, Ohio State University, Columbus, OH 43210, USA
Diabetes 57:635-44. 2008..We tested the hypothesis that activating transcription factor 3 (ATF3), a stress-inducible proapoptotic gene, downregulates the expression of IRS2 in beta-cells...
Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2Jinhua Wu
Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute, and Department of Pharmacology, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
Nat Struct Mol Biol 15:251-8. 2008..Although Tyr628 was phosphorylated by the insulin receptor, its catalytic turnover was poor, resulting in kinase inhibition. Our studies indicate that the KRLB region functions to limit tyrosine phosphorylation of IRS2...
Defective insulin secretion in pancreatic beta cells lacking type 1 IGF receptorShouhong Xuan
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York, USA
J Clin Invest 110:1011-9. 2002..These observations reveal a requirement of IGF1R-mediated signaling for insulin secretion...
RIP-Cre revisited, evidence for impairments of pancreatic beta-cell functionJi-Yeon Lee
Laboratory of Genetics and Physiology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 281:2649-53. 2006..In addition, we review the use of RIP-Cre mice and discuss possible molecular underpinnings and ramifications of our findings...
Insulin receptor substrate 2 plays diverse cell-specific roles in the regulation of glucose transportMarianna Sadagurski
Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
J Biol Chem 280:14536-44. 2005..These observations suggest that IRS-2 functions as a negative or positive regulator of glucose transport in a cell-specific manner. Our results also show that IRS-2 function depends on its cell-specific association with PI 3-kinase...
Suppression of insulin receptor substrate 1 (IRS-1) promotes mammary tumor metastasisZhefu Ma
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Mol Cell Biol 26:9338-51. 2006..Collectively, our findings reveal that inactivation of IRS-1 enhances breast cancer metastasis and support the novel hypothesis that IRS-1 has metastasis suppressor functions for breast cancer...
Genetic deficiency of glycogen synthase kinase-3beta corrects diabetes in mouse models of insulin resistanceKatsuya Tanabe
Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St Louis, Missouri, United States of America
PLoS Biol 6:e37. 2008..These results thus form the rationale for developing agents to inhibit this enzyme in obese insulin-resistant individuals to preserve beta-cells and prevent diabetes onset...
Research Grants
- INTERACTION BETWEEN INSULIN RECEPTORS AND CELL PROTEINSMorris White; Fiscal Year: 1993..These experiments will provide new information regarding the molecular basis for interactions between the IR and cellular protein, and provide a model to understand the mechanism of insulin receptor signal transmission...
- Regulating IRS-proteins by Ser/Thr PhosphorylationMorris F White; Fiscal Year: 2010....
- IRS-2 FUNCTION IN BETA CELL PHYSIOLOGYMorris White; Fiscal Year: 2004....
- REGULATION AND FUNCTION OF IRS-PROTEINSMorris White; Fiscal Year: 2003..This work might highlight IRS-proteins as ideal targets for inhibition of tumor growth. ..
- IRS2 function in beta cell physiologyMorris F White; Fiscal Year: 2010..3. Establish the relation between T-cell infiltration and Irs2 signaling in beta-cells of the NOD mouse. 4. Investigate the mechanism of Irs2-dependent beta-cell regeneration. ..
- Regulating IRS-proteins by Ser/Thr PhosphorylationMorris White; Fiscal Year: 2009....
- Regulating IRS-proteins by Ser/Thr PhosphorylationMorris White; Fiscal Year: 2007....
- IRS2 function in beta cell physiologyMorris White; Fiscal Year: 2007..3. Establish the relation between T-cell infiltration and Irs2 signaling in beta-cells of the NOD mouse. 4. Investigate the mechanism of Irs2-dependent beta-cell regeneration. ..
- STRUCTURE AND FUNCTION OF THE IRS SIGNALING SYSTEMMorris White; Fiscal Year: 1999....
- FUNCTION OF THE INSULIN RECEPTOR SUBSTRATE PP185Morris White; Fiscal Year: 1993....
- INTERACTION BETWEEN INSULIN RECEPTORS AND CELL PROTEINSMorris White; Fiscal Year: 1999....
