IRS-2

Summary

Gene Symbol: IRS-2
Description: insulin receptor substrate 2
Alias: IRS-2, insulin receptor substrate 2
Species: human

Top Publications

  1. ncbi Defects of the insulin receptor substrate (IRS) system in human metabolic disorders
    G Sesti
    Department of Experimental and Clinical Medicine, University of Catanzaro Magna Graecia, 88100 Catanzaro, Italy
    FASEB J 15:2099-111. 2001
  2. ncbi SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2
    Liangyou Rui
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 277:42394-8. 2002
  3. ncbi Clearance of HCV improves insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate 1 and 2
    Takumi Kawaguchi
    Department of Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan
    Am J Gastroenterol 102:570-6. 2007
  4. ncbi Insulin-like growth factor I receptor signaling and nuclear translocation of insulin receptor substrates 1 and 2
    Hongzhi Sun
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Mol Endocrinol 17:472-86. 2003
  5. ncbi Estrogen receptor-alpha regulates the degradation of insulin receptor substrates 1 and 2 in breast cancer cells
    Catia Morelli
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Oncogene 22:4007-16. 2003
  6. ncbi IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2 association in human monocytes: relationship with the inhibitory effect of IL-13 on ROI production
    P Sozzani
    Laboratoire de l Université P Sabatier, CHU Rangueil, Toulouse, France
    Biochem Biophys Res Commun 244:665-70. 1998
  7. ncbi Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries
    H W Yen
    Department of Obstetrics and Gynecology, Cedars Sinai Burns and Allen Research Institute, Cedars Sinai Medical Center The David Geffen School of Medicine at UCLA, 8700 Beverly Blvd, Davis 2066, Los Angeles, CA 90048, USA
    Mol Hum Reprod 10:473-9. 2004
  8. pmc Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR
    Alexandros Tzatsos
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA
    J Biol Chem 284:22525-34. 2009
  9. doi Insulin receptor substrate (IRS)-2, not IRS-1, protects human neuroblastoma cells against apoptosis
    Bhumsoo Kim
    Department of Neurology, University of Michigan, 5371 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109 2200, USA
    Apoptosis 14:665-73. 2009
  10. ncbi siRNA-based gene silencing reveals specialized roles of IRS-1/Akt2 and IRS-2/Akt1 in glucose and lipid metabolism in human skeletal muscle
    Karim Bouzakri
    Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Cell Metab 4:89-96. 2006

Research Grants

  1. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2011
  2. Morris F White; Fiscal Year: 2014
  3. Gene and environment interaction and insulin resistance
    Raquel Villegas; Fiscal Year: 2013
  4. RAMON E PARSONS; Fiscal Year: 2016
  5. Morris F White; Fiscal Year: 2016
  6. Joseph A Baur; Fiscal Year: 2016
  7. The In Vivo Role of JNK-1 and IRS-1 Ser307 Phosphorylation In Development of Insu
    Umut Ozcan; Fiscal Year: 2012
  8. Role of the KRLB region in regulating IRS2 function
    KATHARINE ELAINE D apos AQUINO; Fiscal Year: 2010
  9. Carlos Fernandez Hernando; Fiscal Year: 2016
  10. JOSE RAUL MERCADO-MATOS; Fiscal Year: 2016

Detail Information

Publications194 found, 100 shown here

  1. ncbi Defects of the insulin receptor substrate (IRS) system in human metabolic disorders
    G Sesti
    Department of Experimental and Clinical Medicine, University of Catanzaro Magna Graecia, 88100 Catanzaro, Italy
    FASEB J 15:2099-111. 2001
    ..In contrast, polymorphisms of the other IRS genes do not appear to contribute to type 2 diabetes...
  2. ncbi SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2
    Liangyou 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...
  3. ncbi Clearance of HCV improves insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate 1 and 2
    Takumi Kawaguchi
    Department of Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan
    Am J Gastroenterol 102:570-6. 2007
    ..The aim of this study is to examine the effects of clearance of HCV on insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate (IRS)1/2, central molecules for insulin signaling...
  4. ncbi Insulin-like growth factor I receptor signaling and nuclear translocation of insulin receptor substrates 1 and 2
    Hongzhi Sun
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Mol Endocrinol 17:472-86. 2003
    ..The interaction of nuclear IRS proteins with upstream binding factor 1 constitutes the first direct link of these proteins with the ribosomal DNA transcription machinery...
  5. ncbi Estrogen receptor-alpha regulates the degradation of insulin receptor substrates 1 and 2 in breast cancer cells
    Catia Morelli
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Oncogene 22:4007-16. 2003
    ..The stabilization of IRS-1 in MDA-MB-231/ER cells was paralleled by the upregulation of the IRS-1/Akt/GSK-3 pathway and improved survival in the presence of IGF-I, whereas IRS-2 was not involved in IGF-I signaling...
  6. ncbi IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2 association in human monocytes: relationship with the inhibitory effect of IL-13 on ROI production
    P Sozzani
    Laboratoire de l Université P Sabatier, CHU Rangueil, Toulouse, France
    Biochem Biophys Res Commun 244:665-70. 1998
    ..We demonstrate for the first time that IL-13 induces the association of IRS-2 with PLC-gamma 1. We proposed here that PLC-gamma 1 is a new candidate recruited by IRS-2...
  7. ncbi Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries
    H W Yen
    Department of Obstetrics and Gynecology, Cedars Sinai Burns and Allen Research Institute, Cedars Sinai Medical Center The David Geffen School of Medicine at UCLA, 8700 Beverly Blvd, Davis 2066, Los Angeles, CA 90048, USA
    Mol Hum Reprod 10:473-9. 2004
    ....
  8. pmc Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR
    Alexandros Tzatsos
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA
    J Biol Chem 284:22525-34. 2009
    ..Overall, these data provide new insights in the molecular mechanisms by which mTORC1 inhibits PI 3-kinase/Akt signaling at the level of IRS-1 and suggest that mTOR signaling toward Akt is scaffold-dependent...
  9. doi Insulin receptor substrate (IRS)-2, not IRS-1, protects human neuroblastoma cells against apoptosis
    Bhumsoo Kim
    Department of Neurology, University of Michigan, 5371 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109 2200, USA
    Apoptosis 14:665-73. 2009
    ....
  10. ncbi siRNA-based gene silencing reveals specialized roles of IRS-1/Akt2 and IRS-2/Akt1 in glucose and lipid metabolism in human skeletal muscle
    Karim Bouzakri
    Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Cell Metab 4:89-96. 2006
    ....
  11. ncbi 4PS/insulin receptor substrate (IRS)-2 is the alternative substrate of the insulin receptor in IRS-1-deficient mice
    M E Patti
    Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    J Biol Chem 270:24670-3. 1995
    ..In IRS-1-deficient mice, 4PS/IRS-2 provides signal transduction to these two major pathways of insulin signaling...
  12. ncbi Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome
    S A El Mkadem
    Molecular Endocrinology Laboratory, Institut Universitaire de Recherche Cilnique, Montpellier, France
    Diabetes 50:2164-8. 2001
    ..0085, OR 1.7, 95% CI 1.09-2.99). We conclude that polymorphic alleles of both IRS-1 and IRS-2, alone or in combination, may have a functional impact on the insulin-resistant component of PCOS...
  13. pmc Insulin receptor substrate-1/2 mediates IL-4-induced migration of human airway epithelial cells
    Steven R White
    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
    Am J Physiol Lung Cell Mol Physiol 297:L164-73. 2009
    ..These data demonstrate that IL-4 can accelerate migration of differentiated AEC after injury. This reparative response does not require STAT6 activation, but rather requires IRS-1 and/or IRS-2...
  14. doi Genome-wide SNP genotyping study using pooled DNA to identify candidate markers mediating susceptibility to end-stage renal disease attributed to Type 1 diabetes
    D W Craig
    Translational Genomics Research Institute, Phoenix, AZ 85004, USA
    Diabet Med 26:1090-8. 2009
    ....
  15. pmc The double-stranded RNA-dependent protein kinase differentially regulates insulin receptor substrates 1 and 2 in HepG2 cells
    Xuerui Yang
    Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, USA
    Mol Biol Cell 21:3449-58. 2010
    ..In summary, we found for the first time that initially known as a virus infection response gene, PKR regulates the upstream central transmitters of insulin signaling, IRS1 and IRS2, through different mechanisms...
  16. ncbi Insulin-like growth factor I (IGF-I)-stimulated pancreatic beta-cell growth is glucose-dependent. Synergistic activation of insulin receptor substrate-mediated signal transduction pathways by glucose and IGF-I in INS-1 cells
    S R Hugl
    Departments of Internal Medicine and Pharmacology, Gifford Laboratories for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, Texas 75235 8854, USA
    J Biol Chem 273:17771-9. 1998
    ..The glucose dependence of IGF-I mediated INS-1 cell proliferation emphasizes beta-cell signaling mechanisms are rather unique in being tightly linked to glycolytic metabolic flux...
  17. ncbi Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK kinases
    J A Johnston
    Lymphocyte Cell Biology Section, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 270:28527-30. 1995
    ..Therefore, these data indicate that IRS-1 and IRS-2 may have important roles in T lymphocyte activation not only in response to IL-4, but also in response to IL-2, IL-7, and IL-15...
  18. ncbi The proto-oncogene product c-Crk associates with insulin receptor substrate-1 and 4PS. Modulation by insulin growth factor-I (IGF) and enhanced IGF-I signaling
    D Beitner-Johnson
    Diabetes Branch, NIDDK Laboratory of Cellular and Molecular Biology, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 271:9287-90. 1996
    ..The levels of IGF-I-induced mitogenesis were proportional to the level of Crk expression. These results suggest that Crk is a positive effector of IGF-I signaling, and may mediate its effects via interaction with IRS-1 and/or 4PS...
  19. ncbi Relationship of insulin receptor substrate-1 and -2 genotypes to phenotypic features of polycystic ovary syndrome
    David A Ehrmann
    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 87:4297-300. 2002
    ..Thus, individuals with the common IRS-2 Gly/Gly genotype may be at increased risk of developing type 2 diabetes...
  20. ncbi Increased insulin resistance in obese children who have both 972 IRS-1 and 1057 IRS-2 polymorphisms
    Sophie Le Fur
    Department of Pediatric Endocrinology, Hopital Saint Vincent de Paul, Universite Paris V, Paris, France
    Diabetes 51:S304-7. 2002
    ..Our results stress the need for combined genotype analysis when candidate genes are functionally involved in the same pathway...
  21. ncbi Grb10 inhibits insulin-stimulated insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase/Akt signaling pathway by disrupting the association of IRS-1/IRS-2 with the insulin receptor
    Kerilyn R Wick
    Department of Pharmacology, The University of Texas Health Science Center, San Antonio 78229, USA
    J Biol Chem 278:8460-7. 2003
    ..We conclude that binding of hGrb10gamma to IR decreases signaling through the IRS/PI 3-kinase/AKT pathway by physically blocking IRS access to IR...
  22. 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
    ..Our data suggest that SH2-B is a novel mediator of the PI 3-kinase pathway in response to leptin or other hormones and cytokines that activate JAK2...
  23. ncbi 14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain
    T Ogihara
    Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7 3 1, Hongo, Bunkyo ku, Tokyo 113, Japan
    J Biol Chem 272:25267-74. 1997
    ..Thus, the association with 14-3-3 protein may play a role in the regulation of insulin sensitivity by interrupting the association between the insulin receptor and IRS-1...
  24. ncbi The IRS-signalling system: a network of docking proteins that mediate insulin action
    M F White
    Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    Mol Cell Biochem 182:3-11. 1998
    ....
  25. pmc Association of insulin receptor substrate proteins with Bcl-2 and their effects on its phosphorylation and antiapoptotic function
    H Ueno
    Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo 113, Japan
    Mol Biol Cell 11:735-46. 2000
    ..Our results indicate that IRS proteins transmit signals from the insulin receptor to Bcl-2, thus regulating cell survival probably through regulating phosphorylation of Bcl-2...
  26. ncbi Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus
    Matthew E Hartman
    Department of Animal Sciences, University of Illinois at Urbana Champaign, 506 South Mathews, Urbana, IL 61801, USA
    J Biol Chem 279:28045-50. 2004
    ....
  27. ncbi Prostate cancer risk and IRS1, IRS2, IGF1, and INS polymorphisms: strong association of IRS1 G972R variant and cancer risk
    Susan L Neuhausen
    Department of Medicine, Division of Epidemiology, University of California Irvine, Irvine, CA 92697 7550, USA
    Prostate 64:168-74. 2005
    ..We hypothesized that functional polymorphisms in INS, IRS1, IRS2, and IGF1 may be associated with prostate cancer...
  28. pmc Overexpression of insulin receptor substrate-2 in human and murine hepatocellular carcinoma
    Mathieu Boissan
    INSERM U 680, Universitié Pierre et Marie Curie, Paris, France
    Am J Pathol 167:869-77. 2005
    ..The emergence of IRS-2 overexpression at preneoplastic stages during experimental hepatocarcinogenesis and its protective effect against apoptosis suggest that IRS-2 contributes to liver tumor progression...
  29. ncbi PPARgamma and colon and rectal cancer: associations with specific tumor mutations, aspirin, ibuprofen and insulin-related genes (United States)
    Martha L Slattery
    Health Research Center, University of Utah, Salt Lake City, 84108, USA
    Cancer Causes Control 17:239-49. 2006
    ..These data suggest that PPARgamma may be associated with many aspects of colorectal cancer including insulin- and inflammation-related mechanisms...
  30. ncbi Oncogenic transformation by the signaling adaptor proteins insulin receptor substrate (IRS)-1 and IRS-2
    Robert K Dearth
    Breast Center, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
    Cell Cycle 6:705-13. 2007
    ..In this review we will discuss the role of IRSs in both transformation and cancer progression...
  31. pmc Insulin receptor substrate-2 mediated insulin-like growth factor-I receptor overexpression in pancreatic adenocarcinoma through protein kinase Cdelta
    Junhye Kwon
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Cancer Res 69:1350-7. 2009
    ..Overall, these findings suggest a novel regulatory role of IRS-2 on the expression of IGF-IR through PKCdelta and mTOR in pancreatic cancer cells...
  32. ncbi Is there an association between variants in candidate insulin pathway genes IGF-I, IGFBP-3, INSR, and IRS2 and risk of colorectal cancer in the Iranian population?
    Khatoon Karimi
    Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran E mail
    Asian Pac J Cancer Prev 14:5011-6. 2013
    ..In this study, we hypothesized that polymorphisms in the genes involving the insulin pathway are associated with risk of CRC...
  33. ncbi Role of IRS-2 in insulin and cytokine signalling
    X J Sun
    Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 377:173-7. 1995
    ..IRS-2 is expressed in many cells, including tissues from IRS-1-/- mice, and may be essential for signalling by several receptor systems...
  34. ncbi Disruption of IRS-2 causes type 2 diabetes in mice
    D J Withers
    Howard Hughes Medical Institute, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 391:900-4. 1998
    ..Our results indicate that dysfunction of IRS-2 may contribute to the pathophysiology of human type 2 diabetes...
  35. ncbi Interaction between the G1057D variant of IRS-2 and overweight in the pathogenesis of type 2 diabetes
    S Mammarella
    Department of Oncology and Neurosciences, Section of Molecular Pathology, University Gabriele D Annunzio, Chieti, Italy
    Hum Mol Genet 9:2517-21. 2000
    ..Carriers of this polymorphism may represent an elective target for prevention of type 2 diabetes through preventing or treating excessive weight...
  36. ncbi Polymorphisms of the insulin receptor substrate-2 in patients with type 2 diabetes
    Rossella D'Alfonso
    Laboratory of Molecular Medicine, Department of Internal Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
    J Clin Endocrinol Metab 88:317-22. 2003
    ..These results strongly argue against a major role of IRS-2 polymorphisms in the pathogenesis of type 2 diabetes...
  37. ncbi Complex haplotypes of IRS2 gene are associated with severe obesity and reveal heterogeneity in the effect of Gly1057Asp mutation
    Corinne Lautier
    Molecular Endocrinology Laboratory, University Institute of Clinical Research, Faculty of Medicine, 641 Avenue du Doyen Gaston Giraud, 34093, Montpellier Cedex 5, France
    Hum Genet 113:34-43. 2003
    ....
  38. ncbi Insulin-like growth factor pathway polymorphisms associated with body size in Hispanic and non-Hispanic white women
    Carol Sweeney
    Health Research Center, Family and Preventive Medicine, University of Utah, Suite A, 375 Chipeta Way, Salt Lake City, UT 84108, USA
    Cancer Epidemiol Biomarkers Prev 14:1802-9. 2005
    ..These results provide evidence that IGF pathway polymorphisms have functional effects on growth and central obesity and indicate that genotype-phenotype relationships are ethnic specific...
  39. ncbi Polymorphisms in insulin-related genes predispose to specific KRAS2 and TP53 mutations in colon cancer
    Wade S Samowitz
    Department of Pathology, University of Utah, Salt Lake City, UT 84108, USA
    Mutat Res 595:117-24. 2006
    ....
  40. ncbi The G1057D polymorphism of IRS-2 gene and its relationship with obesity in conferring susceptibility to type 2 diabetes in Asian Indians
    D Bodhini
    Madras Diabetes Research Foundation and Dr Mohan s Diabetes Specialities Centre, Gopalapuram, Chennai, India
    Int J Obes (Lond) 31:97-102. 2007
    ..To investigate the association of insulin receptor substrate-2 (IRS-2) G1057D polymorphism with type 2 diabetes and obesity in Asian Indians...
  41. pmc Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor substrate 1 (IRS-1) or IRS-2
    Robert K Dearth
    Breast Cancer, Baylor College of Medicine and Methodist Hospital, Department of Medicine, Houston, TX 77030, USA
    Mol Cell Biol 26:9302-14. 2006
    ..This study defines IRSs as oncogene proteins in vivo and provides new models to develop inhibitors against IRSs for anticancer therapy...
  42. ncbi Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States
    M L Slattery
    University of Utah, Salt Lake City, Utah 84108, USA
    Breast Cancer Res Treat 104:197-209. 2007
    ..An insulin-related pathway to breast cancer has been hypothesized...
  43. ncbi Divergent roles for IRS-1 and IRS-2 in breast cancer metastasis
    Shannon L Gibson
    Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Cell Cycle 6:631-7. 2007
    ..Understanding how the IRS proteins function in tumor progression is essential for future efforts aimed at developing approaches to target IRS-1 and IRS-2 in a diagnostic or therapeutic manner for the benefit of breast cancer patients...
  44. ncbi Insulin pathway related genes and risk of colorectal cancer: INSR promoter polymorphism shows a protective effect
    Sonali Pechlivanis
    Division of Molecular Genetic Epidemiology, German Cancer Research Center DKFZ, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
    Endocr Relat Cancer 14:733-40. 2007
    ..28, 95% CI 0.11-0.70). SNPs in the INS, IGFBPI, and IRS2 genes did not affect the risk of CRC. In conclusion, genetic variation in the insulin signaling pathway genes may affect the risk of CRC...
  45. pmc Leptin and leptin receptor genotypes and colon cancer: gene-gene and gene-lifestyle interactions
    Martha L Slattery
    Department of Medicine, University of Utah, Salt Lake City, UT, USA
    Int J Cancer 122:1611-7. 2008
    ..VDR polymorphisms interacted with all LEP and LEPR polymorphisms. These data support an association between LEP and colon cancer. They also suggest that the mechanisms linking leptin to colon cancer may be independent of energy balance...
  46. pmc Genetic variation in candidate obesity genes ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1 and risk for breast cancer in the Cancer Prevention Study II
    Heather Spencer Feigelson
    Department of Epidemiology and Surveillance Research, American Cancer Society, Williams Street, NW, Atlanta, Georgia 30303 1002, USA
    Breast Cancer Res 10:R57. 2008
    ..Obesity has consistently been associated with postmenopausal breast cancer risk. Proteins that are secreted by adipose tissue or are involved in regulating body mass may play a role in breast tumor development...
  47. pmc Insulin-like growth factor-1- and interleukin-6-related gene variation and risk of multiple myeloma
    Brenda M Birmann
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 18:282-8. 2009
    ..Nonetheless, the data are consistent with the hypothesis that IGF-1- and IL-6-related gene variation influences susceptibility to multiple myeloma and warrant confirmation in larger populations...
  48. doi Insulin receptor substrate-2 gene polymorphism: is it associated with endometrial cancer?
    Filiz Cayan
    Departments of Obstetrics and Gynecology, University of Mersin School of Medicine, Mersin, Turkey
    Gynecol Endocrinol 26:378-82. 2010
    ..However little is known about its possible association with cancer. To investigate this association, we determined the distribution of its genotypes and frequency of alleles in endometrial cancer patients...
  49. doi Insulin-like growth factor axis gene polymorphisms modify risk of pancreatic cancer
    Xiaoqun Dong
    Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States
    Cancer Epidemiol 36:206-11. 2012
    ..We hypothesized that IGF-axis genetic variants modify individual susceptibility to pancreatic cancer...
  50. pmc IRS2 is a candidate driver oncogene on 13q34 in colorectal cancer
    Elizabeth Day
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Int J Exp Pathol 94:203-11. 2013
    ..Together, these data identify IRS2 as a likely driver oncogene in the prevalent 13q34 region of gain/amplification and suggest that IRS2 over-expression may provide an additional mechanism of PI3 kinase pathway activation in CRC...
  51. ncbi Variations in insulin secretion in carriers of gene variants in IRS-1 and -2
    Leen M 't Hart
    Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
    Diabetes 51:884-7. 2002
    ..We conclude that the common gene variants in IRS-1 and IRS-2 are not associated with altered glucose-stimulated insulin secretion in two populations from the Netherlands...
  52. ncbi Associations among IRS1, IRS2, IGF1, and IGFBP3 genetic polymorphisms and colorectal cancer
    Martha L Slattery
    Health Research Center, School of Medicine, University of Utah, Salt Lake City, 84108, USA
    Cancer Epidemiol Biomarkers Prev 13:1206-14. 2004
    ..We hypothesize that genetic polymorphisms of insulin receptor substrates (IRS-1 and IRS-2), IGF-I, and IGFBP-3 alter colorectal cancer risk because of their roles in the insulin-related signaling pathway...
  53. ncbi The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer
    Kerstin Wagner
    Division of Molecular Genetic Epidemiology C050, German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    Carcinogenesis 25:2473-8. 2004
    ..54, 95% CI 0.32-0.89, P = 0.01). A genotype combination analysis of the non-synonymous polymorphisms in the IRS1, IRS2 and SHC1 genes did not show any effect on breast cancer risk...
  54. ncbi Expression profiling of macrophages from subjects with atherosclerosis to identify novel susceptibility genes
    Daniel A Hägg
    Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Goteborg, Goteborg, Sweden
    Int J Mol Med 21:697-704. 2008
    ..Our method provides a reliable approach for identifying susceptibility genes for atherosclerosis, and we conclude that elevated IRS2 gene expression in macrophages may be associated with an increased risk of CHD...
  55. pmc Genetic deficiency of glycogen synthase kinase-3beta corrects diabetes in mouse models of insulin resistance
    Katsuya 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
    ..In the second model, mice missing two alleles of the insulin receptor substrate 2 (Irs2-/-), like the Ir+/- mice, are insulin resistant, but develop profound beta-cell loss, resulting ..
  56. ncbi Overexpression of insulin receptor substrate-1, but not insulin receptor substrate-2, protects a T cell hybridoma from activation-induced cell death
    Li Li
    Department of Immunology, Jerome Holland Laboratories, American Red Cross, Rockville, MD 20852, USA
    J Immunol 168:6215-23. 2002
    ..1 cells from AICD by diminishing FasL transcription through a pathway that is independent of the tyrosine phosphorylation of IRS1 and phosphatidylinositol 3'-kinase activity...
  57. ncbi Role of central nervous system and ovarian insulin receptor substrate 2 signaling in female reproductive function in the mouse
    Irina Neganova
    Centre for Diabetes and Endocrinology, Rayne Institute, University College London, London WC1E 6JJ, United Kingdom
    Biol Reprod 76:1045-53. 2007
    ..Our data suggest that ovarian rather than central nervous system IRS2 signaling is important in the regulation of female reproductive function...
  58. ncbi Interaction of insulin receptor substrate 3 with insulin receptor, insulin receptor-related receptor, insulin-like growth factor-1 receptor, and downstream signaling proteins
    P Xu
    Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 274:15262-70. 1999
    ..Thus, in contrast to other IRS proteins, mIRS3 appears to have greater specificity for activation of the phosphatidylinositol 3-kinase pathway rather than the Grb2/Ras pathway...
  59. ncbi Modulation of radiation response by inhibiting topoisomerase II catalytic activity
    Santiago Mateos
    Department of Cell Biology, Cell Culture and Radiobiology Research Group, University of Seville, Avda Reina Mercedes n degree 6, 41012 Seville, Spain
    Mutat Res 599:105-15. 2006
    ..The mechanism of radiation enhancement may involve a direct or indirect participation of topo II in the repair of radiation-induced DNA damage...
  60. ncbi Aspirin, NSAIDs, and colorectal cancer: possible involvement in an insulin-related pathway
    Martha L Slattery
    Health Research Center and Department of Pathology, School of Medicine, University of Utah, 375 Chipeta Way, Suite A, Salt Lake City, UT 84108, USA
    Cancer Epidemiol Biomarkers Prev 13:538-45. 2004
    ..We explore the associations between aspirin/NSAIDs, the insulin-related pathway, and the risk of colorectal cancer...
  61. ncbi A role for the insulin-interleukin (IL)-4 receptor motif of the IL-4 receptor alpha-chain in regulating activation of the insulin receptor substrate 2 and signal transducer and activator of transcription 6 pathways. Analysis by mutagenesis
    H Y Wang
    Department of Immunology, Jerome Holland Labs, American Red Cross, Rockville, Maryland 20855, USA
    J Biol Chem 273:9898-905. 1998
    ..Taken together, these results indicate the important role of the I4R motif in regulating IRS docking and suggest that I4R docking to a PTB domain-containing protein regulates activation of the STAT6 pathway...
  62. ncbi Isolation of camptothecin-sensitive chinese hamster cell mutants: phenotypic heterogeneity within the ataxia telangiectasia-like XRCC8 (irs2) complementation group
    M A Johnson
    School of Biological Sciences, Donnan Laboratories, University of Liverpool, Liverpool L69 7ZD, UK
    Mutagenesis 15:367-74. 2000
    ....
  63. ncbi Reversal of denervation-induced insulin resistance by SHIP2 protein synthesis blockade
    Daniela F Bertelli
    Department of Physiology and Biophysics, University of Campinas 6040 Campinas SP, Brazil
    Am J Physiol Endocrinol Metab 284:E679-87. 2003
    ..Thus modulation of the functional status of SHIP2 may be a major mechanism of insulin resistance induced by denervation...
  64. doi Cinnamon extract inhibits the postprandial overproduction of apolipoprotein B48-containing lipoproteins in fructose-fed animals
    Bolin Qin
    Beltsville Human Nutrition Research Center, Agricultural Research Service, U S Department of Agriculture, Beltsville, MD 20705, USA
    J Nutr Biochem 20:901-8. 2009
    ....
  65. ncbi The roles of phosphatidylinositol 3-kinase and protein kinase Czeta for thrombopoietin-induced mitogen-activated protein kinase activation in primary murine megakaryocytes
    P Rojnuckarin
    Division of Hematology, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Biol Chem 276:41014-22. 2001
    ..These data demonstrate a novel role of PI3K and PKCzeta in steady-state megakaryopoiesis...
  66. pmc Beta cell-specific deficiency of the stimulatory G protein alpha-subunit Gsalpha leads to reduced beta cell mass and insulin-deficient diabetes
    Tao Xie
    Metabolic Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 104:19601-6. 2007
    ..Studies have suggested that G(s)alpha/cAMP mediates these actions by stimulating insulin receptor substrate 2 (IRS2) expression...
  67. pmc Extracts of Rehmanniae radix, Ginseng radix and Scutellariae radix improve glucose-stimulated insulin secretion and beta-cell proliferation through IRS2 induction
    Sun Min Park
    Department of Food and Nutrition, College of Natural Science, Hoseo University, 165 Sechul ri, Baebang myun, Asan Si, Chungchongnam do, 336 795, Republic of Korea
    Genes Nutr 2:347-51. 2008
    ..Increased PDX-1 expression was associated with beta-cell proliferation, which was consistent with the cell viability assay. In conclusion, R. radix, Ginseng radix and S. radix had an insulinotropic action similar to that of exendin-4...
  68. ncbi The isolation and genetic analysis of V79-derived etoposide sensitive Chinese hamster cell mutants: two new complementation groups of etoposide sensitive mutants
    M A Johnson
    School of Biological Sciences, Donnan Laboratories, University of Liverpool, Liverpool, UK
    Mutat Res 435:271-82. 1999
    ..This study indicates that cellular responses to topoisomerase II inhibitors are complex and hypersensitivity may result from mutations in many different genes...
  69. pmc Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure
    Alfonso Mora
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 385:639-48. 2005
    ..other insulin-controlled genes, namely IGFBP1 (insulin-like-growth-factor-binding protein-1), IRS2 (insulin receptor substrate 2) and glucokinase, were regulated abnormally by feeding in the liver of PDK1-deficient mice...
  70. ncbi Huang-Lian-Jie-Du-Tang supplemented with Schisandra chinensis Baill. and Polygonatum odoratum Druce improved glucose tolerance by potentiating insulinotropic actions in islets in 90% pancreatectomized diabetic rats
    Sunmin Park
    Deptartment of Food and Nutrition, College of Natural Science, Hoseo University, Asan Si, Korea
    Biosci Biotechnol Biochem 73:2384-92. 2009
    ..The rise in hyperplasia was associated with elevated IRS2 and PDX-1 expression in the islets. In conclusion, HLJDT-M worked as an anti-diabetic prescription by enhancing insulinotropic actions in diabetic rats...
  71. pmc Insulin receptor substrate-2 in beta-cells decreases diabetes in nonobese diabetic mice
    Lisa 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...
  72. pmc Insulin receptor substrate 2 plays a crucial role in beta cells and the hypothalamus
    Naoto Kubota
    Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
    J Clin Invest 114:917-27. 2004
    We previously demonstrated that insulin receptor substrate 2 (Irs2) KO mice develop diabetes associated with hepatic insulin resistance, lack of compensatory beta cell hyperplasia, and leptin resistance...
  73. doi Chlorpromazine attenuates pancreatic beta-cell function and mass through IRS2 degradation, while exercise partially reverses the attenuation
    S Park
    Department of Food and Nutrition, College of Natural Science, Hoseo University, Asan Si, Korea
    J Psychopharmacol 22:522-31. 2008
    ..This modulation by HCPZ and exercise was associated with increasing intracellular IRS2 protein levels in independent pathways...
  74. doi Fulminant type 1 diabetes mellitus observed in insulin receptor substrate 2 deficient mice
    T Arai
    Department of Veterinary Science, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino, Tokyo, 180 8602, Japan
    Clin Exp Med 8:93-9. 2008
    ..fulminant type 1 diabetes mellitus (DM) accompanying abrupt hyperglycaemia and ketonuria observed in insulin receptor substrate 2 (IRS2)-deficient mice...
  75. doi Identification of a region in the human IRS2 promoter essential for stress induced transcription depending on SP1, NFI binding and ERK activation in HepG2 cells
    M Udelhoven
    Department of Internal Medicine II, Center for Molecular Medicine Cologne CMMC, University of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany
    J Mol Endocrinol 44:99-113. 2010
    ....
  76. pmc Calcineurin signaling regulates human islet {beta}-cell survival
    Scott A Soleimanpour
    Division of Endocrinology, Department of Medicine and The Institute for Diabetes, Obesity, and Metabolism, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 285:40050-9. 2010
    ..These findings reveal calcineurin as a regulator of human β-cell survival in part through regulation of Irs2, with implications for the pathogenesis and treatment of diabetes following organ transplantation...
  77. ncbi Energy balance, insulin-related genes and risk of colon and rectal cancer
    Martha L Slattery
    Health Research Center, University of Utah, Salt Lake City, UT 84108, USA
    Int J Cancer 115:148-54. 2005
    ..Obesity, physical activity and energy intake appear to alter risk of colorectal cancer; however, the risk appears to be minimally influenced by genetic variants evaluated...
  78. pmc Glucokinase and IRS-2 are required for compensatory beta cell hyperplasia in response to high-fat diet-induced insulin resistance
    Yasuo Terauchi
    Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo, Tokyo, Japan
    J Clin Invest 117:246-57. 2007
    ..DNA chip analysis revealed decreased insulin receptor substrate 2 (Irs2) expression in HF diet-fed Gck(+/-) mouse islets compared with wild-type islets...
  79. ncbi Chlorpromazine exacerbates hepatic insulin sensitivity via attenuating insulin and leptin signaling pathway, while exercise partially reverses the adverse effects
    Sunmin Park
    Department of Food and Nutrition, College of Natural Science, Hoseo University, Asan Si, Chungnam Do, Republic of Korea
    Life Sci 80:2428-35. 2007
    ..Enhancement of insulin and leptin signaling through an induction of IRS2 may play an important role in improving hepatic glucose homeostasis...
  80. ncbi Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin, and lipoprotein pathways in enterocytes
    B Qin
    U S Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, Maryland 20705, USA
    Horm Metab Res 41:516-22. 2009
    ..In conclusion, Cinulin PF improves inflammation related intestinal dyslipidemia...
  81. doi Olanzapine, not resperidone, exacerbates beta-cell function and mass in ovariectomized diabetic rats and estrogen replacement reverses them
    Sunmin Park
    Department of Food and Nutrition, Diabetes Obesity Center, College of Natural Science, Hoseo University, Chungnam Do, Korea
    J Psychopharmacol 24:1105-14. 2010
    ..Further human studies are needed to support the claim that olanzapine should be avoided in the treatment of schizophrenic postmenopausal patients with diabetes...
  82. pmc Effect of ovarian cancer ascites on cell migration and gene expression in an epithelial ovarian cancer in vitro model
    Liliane Meunier
    Centre de Recherche du Centre Hospitalier de l Université de Montréal Institut du cancer de Montréal, Montreal, Quebec, Canada
    Transl Oncol 3:230-8. 2010
    ..This study revealed novel candidates that may play a role in ovarian cancer cell migration...
  83. doi Dietary protein deprivation upregulates insulin signaling and inhibits gluconeogenesis in rat liver
    Yuka Toyoshima
    Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo ku, Tokyo 113 8657, Japan
    J Mol Endocrinol 45:329-40. 2010
    ....
  84. pmc Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells
    Shouhong Xuan
    Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    J Biol Chem 285:41044-50. 2010
    ..The insulin and IGF pathways appear to control β cell functions independently and selectively...
  85. ncbi Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling
    D J Withers
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, Massachusetts 02215, USA
    Nat Genet 23:32-40. 1999
    ..Thus, Irs-2 integrates the effects of insulin in peripheral target tissues with Igf-1 in pancreatic beta-cells to maintain glucose homeostasis...
  86. ncbi Role of peroxisome proliferator-activated receptor-gamma in maintenance of the characteristics of mature 3T3-L1 adipocytes
    Yoshikazu Tamori
    Division of Diabetes, 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
    Diabetes 51:2045-55. 2002
    ..These results suggest that PPAR-gamma plays an important role in mature 3T3-L1 adipocytes at least in part by maintaining the expression of genes that confer the characteristics of mature adipocytes...
  87. pmc Involvement of the PA28gamma-dependent pathway in insulin resistance induced by hepatitis C virus core protein
    Hironobu Miyamoto
    Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamadaoka, Suita, Osaka 565 0871, Japan
    J Virol 81:1727-35. 2007
    ..These results suggest that the HCV core protein suppresses insulin signaling through a PA28gamma-dependent pathway...
  88. pmc EPO receptor circuits for primary erythroblast survival
    Pradeep Sathyanarayana
    Stem and Progenitor Cell Biology Program, Molecular Medicine Division, Maine Medical Center Research Institute, Scarborough, ME 04074, USA
    Blood 111:5390-9. 2008
    ..EPOR survival circuits therefore include the repression of Bim plus FoxO3a, and EPOR/PY343/STAT5-dependent stimulation of Pim1, Pim3, Irs2 plus Serpina-3G, and Trb3 as new antiapoptotic effectors...
  89. doi Green tea (-)-epigallocatechin gallate inhibits insulin stimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor pathway
    Hui Chen Ku
    Dept of Life Science, College of Science, National Central Univ, Jhong Li, Taiwan 32054
    Am J Physiol Cell Physiol 297:C121-32. 2009
    ..Moreover, EGCG tended to increase insulin-stimulated associations between the 67LR and IR, IRS1, IRS2, and IRS4 proteins. These data suggest that EGCG mediates anti-insulin signaling in preadipocyte mitogenesis via the 67LR pathway...
  90. pmc Role of atypical protein kinase C in activation of sterol regulatory element binding protein-1c and nuclear factor kappa B (NFkappaB) in liver of rodents used as a model of diabetes, and relationships to hyperlipidaemia and insulin resistance
    M P Sajan
    Research Service, James A Haley Veterans Hospital, Tampa, FL 33612, USA
    Diabetologia 52:1197-207. 2009
    ....
  91. pmc Role of the PI3K/AKT and mTOR signaling pathways in acute myeloid leukemia
    Sophie Park
    Institut Cochin, Departement d Hematologie, CNRS, UMR8104, Paris
    Haematologica 95:819-28. 2010
    ..These results open the way for the design of direct inhibitors of protein synthesis as novel acute myeloid leukemia therapies and also for the development of second generation mTOR inhibitors (the TORKinhibs)...
  92. doi Impairment of insulin receptor signal transduction in placentas of intra-uterine growth-restricted newborns and its relationship with fetal growth
    M E Street
    Department of Paediatrics, University Hospital of Parma, 43126 Parma, Italy
    Eur J Endocrinol 164:45-52. 2011
    ....
  93. ncbi Role of insulin receptor substrate-2 in interleukin-9-dependent proliferation
    J B Demoulin
    Ludwig Institute for Cancer Research and Experimental Medicine Unit, Universite Catholique de Louvain, Brussels, Belgium
    FEBS Lett 482:200-4. 2000
    ..Finally, 32D cells that were transfected with the IL-9 receptor but lack IRS expression survived in the presence of IL-9. Ectopic IRS1 expression allowed for IL-9-induced proliferation, in the absence of significant PKB phosphorylation...
  94. pmc Osmotic regulation of insulin-induced mitogen-activated protein kinase phosphatase (MKP-1) expression in H4IIE rat hepatoma cells
    Mohammad Reza Lornejad-Schäfer
    Medizinische Einrichtungen der Heinrich Heine Universitat, Klinik fur Gastroenterologie, Hepatologie und Infektiologie, Moorenstrasse 5, D 40225 Dusseldorf, Germany
    Biochem J 371:609-19. 2003
    ..The suppression of MKP-1 may further contribute to insulin resistance under dehydrating conditions by allowing unbalanced MAP kinase activation...
  95. pmc Interaction of the protein tyrosine phosphatase PTPL1 with the PtdIns(3,4)P2-binding adaptor protein TAPP1
    Wendy A Kimber
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 376:525-35. 2003
    ..Consistent with this notion we observed RNA-interference-mediated knock-down of TAPP1 in HEK-293 cells, enhanced activation and phosphorylation of PKB following IGF1 stimulation...
  96. ncbi Expression profiling of 11beta-hydroxysteroid dehydrogenase type-1 and glucocorticoid-target genes in subcutaneous and omental human preadipocytes
    I J Bujalska
    Division of Medical Sciences, The Medical School, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
    J Mol Endocrinol 37:327-40. 2006
    ..Our results provide insight into the genes involved in the regulation of adipocyte differentiation by cortisol, highlighting the depot specifically in human adipose tissue...
  97. ncbi Regulation of pancreatic beta-cell regeneration in the normoglycemic 60% partial-pancreatectomy mouse
    Mina Peshavaria
    University of Vermont College of Medicine, Department of Medicine, Given C331, Burlington, VT 05405, USA
    Diabetes 55:3289-98. 2006
    ..These data suggest that the IRS2-Akt pathway mediates compensatory beta-cell growth by activating beta-cell proliferation with an increase in the number of beta-cell clusters/small islets...
  98. ncbi Phenotypes of IRS-2 deficient mice produced by reproductive technology are stable
    Haruo Hashimoto
    Central Institute for Experimental Animals, Kawasaki shi, Kanagawa, Japan
    Exp Anim 56:149-54. 2007
    ..Therefore, we concluded that phenotypes of Irs2(-/-) mice produced by reproductive technology are stable...
  99. doi Proliferation of colo-357 pancreatic carcinoma cells and survival of patients with pancreatic carcinoma are not altered by insulin glargine
    Saskia Erbel
    Department of Internal Medicine I, University of Heidelberg, Heidelberg, Germany
    Diabetes Care 31:1105-11. 2008
    ..Induction of cell proliferation would be particularly relevant for insulin treatment of subjects with diabetes and the potential of bearing tumor cells (e.g., a history of a malignant disease)...
  100. doi Intracerebroventricular injection of citrate inhibits hypothalamic AMPK and modulates feeding behavior and peripheral insulin signaling
    Graziela R Stoppa
    Departamento de Bioquimica, IB, Universidade Estadual de Campinas, Campinas, SP, Brazil
    J Endocrinol 198:157-68. 2008
    ..Moreover, the treatment with citrate for 7 days promoted body weight loss and decreased the adipose tissue. Our results suggest that citrate and glucose may serve as signals of energy and nutrient availability to hypothalamic cells...
  101. pmc Measures of striatal insulin resistance in a 6-hydroxydopamine model of Parkinson's disease
    J K Morris
    Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA
    Brain Res 1240:185-95. 2008
    ..in neuronal tissues is primarily non-insulin dependent, proteins involved in insulin signaling, such as insulin receptor substrate 2 (IRS2) and glucose transporter 4 (GLUT4), are present in the basal ganglia...

Research Grants48

  1. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2011
    ..Moreover, elucidation of the signaling mechanisms that regulate autophagy in cardiomyocytes may lead to novel therapies for preventing or modulating heart injury as occurs in diabetes, cardiac ischemia or cardiac hypertrophy. ..
  2. Morris F White; Fiscal Year: 2014
    ..3. Identify the mTORC1-dependent phosphorylation sites in IRS1 that regulate insulin signaling and glucose tolerance in mice. ..
  3. Gene and environment interaction and insulin resistance
    Raquel Villegas; Fiscal Year: 2013
    ..Findings from this study can be used to aid in the prevention of T2D, since insulin resistance is a reversible condition. ..
  4. RAMON E PARSONS; Fiscal Year: 2016
    ..09/04) Page 4 Form Page 3 ..
  5. Morris F White; Fiscal Year: 2016
    ....
  6. Joseph A Baur; Fiscal Year: 2016
    ....
  7. The In Vivo Role of JNK-1 and IRS-1 Ser307 Phosphorylation In Development of Insu
    Umut Ozcan; Fiscal Year: 2012
    ..Our proposal, by using genetically engineered mouse models, aims to investigate the molecular mechanisms of insulin resistance. ..
  8. Role of the KRLB region in regulating IRS2 function
    KATHARINE ELAINE D apos AQUINO; Fiscal Year: 2010
    ..This information could reveal strategies to reverse the negative consequences of impaired insulin signaling and insulin resistance. ..
  9. Carlos Fernandez Hernando; Fiscal Year: 2016
    ..dehydrogenase (HADHB), key enzymes involved in the regulation of fatty acid oxidation, and insulin receptor substrate 2 (IRS2), which regulates insulin signaling...
  10. JOSE RAUL MERCADO-MATOS; Fiscal Year: 2016
    ..Additionally, our results can provide the rationale for the development of novel therapeutic approaches for the treatment of IRS2-dependent malignancies. ..
  11. CONTROL OF INSULIN BIOSYNTHESIS
    Fumihiko Urano; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The severe postnatal loss of [unreadable]-cells and diabetes in insulin receptor substrate 2 deficient mice (Irs2-/-) has confirmed the necessity of maintaining [unreadable]-cell insulin signaling for ..
  12. STRUCTURAL STUDY OF THE INSULIN RECEPTOR TYROSINE KINASE
    Stevan R Hubbard; Fiscal Year: 2010
    ..By understanding at the molecular level how the insulin receptor is regulated, we hope to facilitate efforts to design small-molecule agonists and inhibitors that could potentially be used as anti-diabetic therapeutics. ..
  13. Leigh Goedeke; Fiscal Year: 2014
    ..In addition, miR-33 also targets the insulin receptor substrate 2 (IRS2), an essential component of the insulin- signaling pathway...
  14. Mechanisms of Glucose-Induced Proliferation in Murine Pancreatic beta Cells
    Laura C Alonso; Fiscal Year: 2010
    ..Whether IRS2 is required or not, either finding will be of significant importance. ..
  15. "Discovery and Development of Anti-Diabetic Drugs."
    GERARD M HOUSEY; Fiscal Year: 2013
    ..Since diabetes is a major disease of substantial proportions world-wide, pharmaceutical products and licensable technologies developed by HPRL will have substantial market opportunities. ..
  16. Role and Activation Status of IRS1/2 in IL-4-induced Protection from Cell Death.
    HOLLY A PORTER; Fiscal Year: 2010
    ..Understanding the molecular programming of a cell may also allow for the better prediction of a patient's response to treatment. ..
  17. Molecular Mechanisms of IL-4 and IL-13 Signaling
    Achsah D Keegan; Fiscal Year: 2010
    ..Our studies will provide a greater understanding of their mechanism of action and contribution to allergic inflammation. This new knowledge could help to develop better approaches to treat allergy and asthma. ..
  18. Aging and Alzheimer's Disease Potential Link with IGF1-R
    Luigi Puglielli; Fiscal Year: 2012
    ..The long-term objective of this proposal is to expand upon our findings and fully characterize the molecular pathway that we have identified. This will allow us to design new pharmacologic approaches for the prevention of AD. ..
  19. Melanocortin-3 receptor regulation of insulin action
    Andrew Butler; Fiscal Year: 2005
    ..The results of these experiments will provide the first definitive evidence that manipulation of the MC3R might be a viable approach for treating insulin resistance. ..
  20. Mechanisms of erythroid differentiation
    PAUL NEY; Fiscal Year: 2009
    ..Irs2 activates some of the same signaling pathways as the distal Epor. So, we will determine whether Irs2 is functionally redundant with the distal Epor in normal erythroid cells. ..
  21. Discovery and development of Antidiabetic Drugs
    GERARD HOUSEY; Fiscal Year: 2003
    ..to establish assay systems to identify and validate small molecules that promote the function of the insulin receptor substrate 2 (IRS2) in mammalian cells...
  22. Mechanism of Fat Induced Hepatic Insulin Resistance
    Varman Samuel; Fiscal Year: 2006
    ..Finally, with a novel method to directly measure gluconeogenesis, we will determine if hepatic fat accumulation increases hepatic gluconeogenesis...
  23. IRS2 function in beta cell physiology
    Morris 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. ..
  24. IRS2 AND B CELL HOMEOSTASIS
    Achsah Keegan; Fiscal Year: 2000
    ....
  25. A Variant in the Betacellulin Gene and Insulin Secretion
    Kristi Silver; Fiscal Year: 2004
    ..In turn, this will lead to new preventative strategies and new molecular targets for the design and effective therapeutic agents. ..
  26. Cyclin D2 Regulation Of Islet Growth
    JAKE KUSHNER; Fiscal Year: 2007
    ..To test if cyclin D2 is an essential regulator of islet growth. 2. To test if Pdx1 influences beta-cell proliferation by regulating cyclin D2. ..
  27. 7th Intl Symposium-Neurobiology/Neuroendocrinology/Aging
    Andrzej Bartke; Fiscal Year: 2004
    ..We are also seeking support for the presenters of the Special Lecture and the Keynote Lecture who will be traveling to Bregenz from the United States. ..
  28. Eighth & Ninth International Symposia on Neurobiology & Neuroendocrinology Aging
    Andrzej Bartke; Fiscal Year: 2007
    ..We are also seeking partial support for the expenses of invited speakers from the United States. [unreadable] [unreadable] [unreadable]..
  29. Aging:Mechanisms & Prevention:34th Annual Meeting of AGE
    Andrzej Bartke; Fiscal Year: 2005
    ..Financial assistance will be provided to those in training to encourage their participation in the meeting. ..
  30. Role of Leptin in Islet Growth
    Rohit Kulkarni; Fiscal Year: 2008
    ..The proposed studies are aimed at the long-term goal of developing therapeutic strategies to prevent or delay the development of diabetes in obese individuals. [unreadable] [unreadable] [unreadable]..
  31. Dissecting the Death Pathway in Islet Beta Cells
    Rohit Kulkarni; Fiscal Year: 2005
    ..abstract_text> ..
  32. CORTICOSTEROID INDUCED APOPTOSIS IN AIRWAY EPITHELIUM
    Steven White; Fiscal Year: 2002
    ..These data would help lead to new therapeutic ideas and modalities in the treatment of asthma to suppress inflammation while preventing mucosal damage. ..
  33. Gordon Conference: Second Messengers and Phosphorylation
    Morris White; Fiscal Year: 2002
    ..To emphasize this goal, four poster presentations that complement the theme of the meeting will be selected for brief oral presentations during the major sessions. ..
  34. FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDY
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2003
    ..C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. ..
  35. REGULATION AND FUNCTION OF IRS-PROTEINS
    Morris White; Fiscal Year: 2004
    ..This work might highlight IRS-proteins as ideal targets for inhibition of tumor growth. ..
  36. INSULIN & GLUCOSE SIGNALING PATHWAYS IN ISLET BETA CELLS
    Rohit Kulkarni; Fiscal Year: 2004
    ....
  37. GENETICS OF CHILDHOOD OBESITY
    Nancy Butte; Fiscal Year: 2004
    ..This QTL method will be implemented in the program package SOLAR using estimation procedures from FISHER. Lastly, we will test for pleiotropic effects of obesity-related QTLs across phenotypes. ..
  38. Nonalcoholic fatty liver disease in Hispanic obese youth
    Nancy Butte; Fiscal Year: 2005
    ..Newly proposed tests include chromogenic assays to measure lipid peroxidation end products and endotoxins, and ELISA and RIA to measure cytokine and markers of systemic inflammation. ..
  39. Leptin modulation of insulin action in the islet b-cell
    Rohit Kulkarni; Fiscal Year: 2005
    ..abstract_text> ..
  40. Regulation of airway epithelial repair
    Steven R White; Fiscal Year: 2010
    ....
  41. Sleep, Metabolic, and Cardiovascular Dysfunction in PCOS
    David Ehrmann; Fiscal Year: 2006
    ..In the other, slow wave activity will be suppressed without awakening the subject and REM sleep will be left undisturbed. Each study will be preceded by 2 nights of basetine sleep. ..
  42. Growth Factors and Colon Cancer
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..This study builds on a unique existing resource to study genetic and environmental associations with colorectal cancer. It will provide insight into colon cancer etiology and therefore avenues to disease prevention. ..
  43. A PROSPECTIVE STUDY OF ALASKA NATIVES & AMERICAN INDIANS
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..The AIAN cohort will serve as a resource to enhance research and training activities of AIAN students interested in health research, health education, and general public health. ..
  44. Islet Transplantation - Protection by Immunobarriers
    Gordon Weir; Fiscal Year: 2007
    ..This work should serve as a guide for the encapsulation and transplantation of xenogeneic islets cells or insulin-producing cells that should eventually be produced from precursor/stem cells. ..
  45. DIET AND SOMATIC MUTATIONS IN COLON CANCER
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2007
    ..e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways. ..
  46. Prediction of Energy Expenditure/Physical Activity in Children and Adolescents
    Nancy Butte; Fiscal Year: 2008
    ..A new method based on direct ambulatory monitoring of HR and PA will be developed to accurately predict EE, and hence 24-h TEE and AEE in children and adolescents. [unreadable] [unreadable]..
  47. Beta Cell Adaptation to Stress in Baboon Pancreas After Partial Pancreatectomy
    FRANCO BATTISTA FOLLI; Fiscal Year: 2010
    ....