C Kahn

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc Lessons on conditional gene targeting in mouse adipose tissue
    Kevin Y Lee
    Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
    Diabetes 62:864-74. 2013
  2. pmc Glypican-4 enhances insulin signaling via interaction with the insulin receptor and serves as a novel adipokine
    Siegfried Ussar
    Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA
    Diabetes 61:2289-98. 2012
  3. pmc Tissue-specific insulin signaling, metabolic syndrome, and cardiovascular disease
    Christian Rask-Madsen
    Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA
    Arterioscler Thromb Vasc Biol 32:2052-9. 2012
  4. pmc Intrinsic differences in adipocyte precursor cells from different white fat depots
    Yazmin Macotela
    Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
    Diabetes 61:1691-9. 2012
  5. pmc Knockout mice challenge our concepts of glucose homeostasis and the pathogenesis of diabetes
    C Ronald Kahn
    Joslin Diabetes Center, Harvard University Medical School, Boston, Massachusetts 02215, USA
    Exp Diabesity Res 4:169-82. 2003
  6. ncbi request reprint Knockout mice challenge our concepts of glucose homeostasis and the pathogenesis of diabetes mellitus
    C R Kahn
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    J Pediatr Endocrinol Metab 13:1377-84. 2000
  7. ncbi request reprint Medicine. Can we nip obesity in its vascular bud?
    C Ronald Kahn
    Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Science 322:542-3. 2008
  8. pmc The Gordon Wilson Lecture. Lessons about the control of glucose homeostasis and the pathogenesis of diabetes from knockout mice
    C Ronald Kahn
    Joslin Diabetes Center, Harvard University Medical School, Boston, Massachusetts, USA
    Trans Am Clin Climatol Assoc 114:125-48. 2003
  9. pmc Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function
    Palle G Laustsen
    Joslin Diabetes Center, Boston, MA 02215, USA
    Mol Cell Biol 27:1649-64. 2007
  10. ncbi request reprint Essential role of insulin receptor substrate-2 in insulin stimulation of Glut4 translocation and glucose uptake in brown adipocytes
    M Fasshauer
    Research Division, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    J Biol Chem 275:25494-501. 2000

Research Grants

  1. Developmental Genes and the Origin of Fat
    C Ronald Kahn; Fiscal Year: 2010
  2. PI 3 KINASE ISOFORMS AND INSULIN ACTION
    C Kahn; Fiscal Year: 2003
  3. GENE EXPRESSION IN DIABETES BY SUBTRACTIVE CLONING
    C Kahn; Fiscal Year: 2003
  4. PI 3-Kinase Isoforms and Insulin Action
    C Kahn; Fiscal Year: 2006
  5. PI 3-Kinase Isoforms in Insulin Action
    C Ronald Kahn; Fiscal Year: 2010
  6. Insulin Receptor Substrates and Insulin Action
    C Ronald Kahn; Fiscal Year: 2010
  7. Developmental Genes and the Origin of Fat
    C Ronald Kahn; Fiscal Year: 2010
  8. PI 3-Kinase Isoforms in Insulin Action
    C Kahn; Fiscal Year: 2009
  9. Developmental Genes and the Origin of Fat
    C Kahn; Fiscal Year: 2009
  10. PI 3-Kinase Isoforms in Insulin Action
    C Kahn; Fiscal Year: 2007

Detail Information

Publications112 found, 100 shown here

  1. pmc Lessons on conditional gene targeting in mouse adipose tissue
    Kevin Y Lee
    Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
    Diabetes 62:864-74. 2013
    ..Thus, different "adipocyte-specific" Cre lines display different degrees of efficiency and specificity, illustrating important differences that must be taken into account in their use for studying adipose biology...
  2. pmc Glypican-4 enhances insulin signaling via interaction with the insulin receptor and serves as a novel adipokine
    Siegfried Ussar
    Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA
    Diabetes 61:2289-98. 2012
    ..In summary, glypican-4 is a novel circulating insulin sensitizing adipose-derived factor that, unlike other insulin sensitizers, acts directly on the insulin receptor to enhance signaling...
  3. pmc Tissue-specific insulin signaling, metabolic syndrome, and cardiovascular disease
    Christian Rask-Madsen
    Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA
    Arterioscler Thromb Vasc Biol 32:2052-9. 2012
    ..Recent advances in our understanding of the complex pathophysiology of insulin's effects on vascular tissues offer new opportunities for preventing these cardiovascular disorders...
  4. pmc Intrinsic differences in adipocyte precursor cells from different white fat depots
    Yazmin Macotela
    Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
    Diabetes 61:1691-9. 2012
    ..Regulation of these populations may provide a new target for the treatment and prevention of obesity and its metabolic complications...
  5. pmc Knockout mice challenge our concepts of glucose homeostasis and the pathogenesis of diabetes
    C Ronald Kahn
    Joslin Diabetes Center, Harvard University Medical School, Boston, Massachusetts 02215, USA
    Exp Diabesity Res 4:169-82. 2003
    ....
  6. ncbi request reprint Knockout mice challenge our concepts of glucose homeostasis and the pathogenesis of diabetes mellitus
    C R Kahn
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    J Pediatr Endocrinol Metab 13:1377-84. 2000
    ....
  7. ncbi request reprint Medicine. Can we nip obesity in its vascular bud?
    C Ronald Kahn
    Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Science 322:542-3. 2008
  8. pmc The Gordon Wilson Lecture. Lessons about the control of glucose homeostasis and the pathogenesis of diabetes from knockout mice
    C Ronald Kahn
    Joslin Diabetes Center, Harvard University Medical School, Boston, Massachusetts, USA
    Trans Am Clin Climatol Assoc 114:125-48. 2003
    ..The result of this work has led us to develop new hypotheses about the nature of the insulin action network...
  9. pmc Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function
    Palle G Laustsen
    Joslin Diabetes Center, Boston, MA 02215, USA
    Mol Cell Biol 27:1649-64. 2007
    ....
  10. ncbi request reprint Essential role of insulin receptor substrate-2 in insulin stimulation of Glut4 translocation and glucose uptake in brown adipocytes
    M Fasshauer
    Research Division, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    J Biol Chem 275:25494-501. 2000
    ..This occurs without effects in differentiation, total activation of Akt and its downstream effectors, but may be caused by alterations in compartmentalization of these downstream signals...
  11. ncbi request reprint Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles
    J C Bruning
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Cell 88:561-72. 1997
    ....
  12. ncbi request reprint A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance
    J C Bruning
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Cell 2:559-69. 1998
    ..Thus, insulin resistance in muscle contributes to the altered fat metabolism associated with type 2 diabetes, but tissues other than muscle appear to be more involved in insulin-regulated glucose disposal than previously recognized...
  13. ncbi request reprint Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
    J C Yoon
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 413:131-8. 2001
    ..These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver...
  14. ncbi request reprint Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes
    R N Kulkarni
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Cell 96:329-39. 1999
    ....
  15. pmc Exercise modulates postreceptor insulin signaling and glucose transport in muscle-specific insulin receptor knockout mice
    J F Wojtaszewski
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 104:1257-64. 1999
    ..The synergistic activation of glucose transport with exercise plus insulin is retained in MIRKO mice, suggesting a phenomenon mediated by nonmuscle cells or by downstream signaling events...
  16. ncbi request reprint A model to explore the interaction between muscle insulin resistance and beta-cell dysfunction in the development of type 2 diabetes
    F Mauvais-Jarvis
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Diabetes 49:2126-34. 2000
    ..These data suggest that muscle, either via changes in substrate availability or by acting as an endocrine tissue, communicates with and regulates insulin sensitivity in other tissues...
  17. pmc Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob/ob) mouse
    N J Kerouz
    Research Division, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 100:3164-72. 1997
    ....
  18. pmc Evidence for a circulating islet cell growth factor in insulin-resistant states
    S N Flier
    Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 98:7475-80. 2001
    ..These data suggest the insulin resistance is associated with a circulating islet cell growth factor that is independent of glucose and obesity...
  19. ncbi request reprint Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene
    E Araki
    Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215
    Nature 372:186-90. 1994
    ..Our results provide evidence for IRS-1-dependent and IRS-1-independent pathways of insulin/IGF-1 signalling and for the existence of an alternative substrate of these receptor kinases...
  20. ncbi request reprint Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alpha
    D A Fruman
    Division of Signal Transduction, Beth Israel Deaconess Medical Center Boston, Massachusetts, USA
    Nat Genet 26:379-82. 2000
    ..Our findings reveal that p55 alpha and/or p50 alpha are required for survival, but not for development of hypoglycaemia, in mice lacking p85 alpha...
  21. ncbi request reprint Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction
    M D Michael
    Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Cell 6:87-97. 2000
    ..Thus, insulin signaling in liver is critical in regulating glucose homeostasis and maintaining normal hepatic function...
  22. ncbi request reprint Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance
    A Zisman
    Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nat Med 6:924-8. 2000
    ..These mice showed severe insulin resistance and glucose intolerance from an early age. Thus, GLUT4-mediated glucose transport in muscle is essential to the maintenance of normal glucose homeostasis...
  23. ncbi request reprint Effects of insulin-sensitising agents in mice with hepatic insulin resistance
    S E Cohen
    Joslin Diabetes Center and Harvard Medical School, One Joslin Place, Boston, MA 02215, USA
    Diabetologia 47:407-11. 2004
    ..To gain insight into the mechanisms of action of these drugs, we compared their actions in two models of insulin resistance: the obese, hyperglycaemic ob/ob mouse and the liver specific insulin receptor knockout (LIRKO) mouse...
  24. pmc Altered function of insulin receptor substrate-1-deficient mouse islets and cultured beta-cell lines
    R N Kulkarni
    Division of Cellular and Molecular Physiology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 104:R69-75. 1999
    ..This article may have been published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org...
  25. pmc The branch point enzyme of the mevalonate pathway for protein prenylation is overexpressed in the ob/ob mouse and induced by adipogenesis
    D Vicent
    Research Division, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    Mol Cell Biol 20:2158-66. 2000
    ....
  26. ncbi request reprint beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass
    R N Kulkarni
    Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, One Joslin Place, Boston Massachusetts 02215, USA
    Nat Genet 31:111-5. 2002
    ..Thus, Igf1r is not crucial for islet beta-cell development, but participates in control of differentiated function...
  27. ncbi request reprint Insulin stimulates serine and tyrosine phosphorylation in the juxtamembrane region of the insulin receptor
    E P Feener
    Joslin Diabetes Center, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts
    J Biol Chem 268:11256-64. 1993
    ..Together with our previous studies, this report suggests that phosphorylation of Tyr960 may play an important role in signal transduction by the insulin receptor...
  28. ncbi request reprint The insulin receptor--a critical link in glucose homeostasis and insulin action
    M E Patti
    Research Division, Joslin Diabetes Center, Boston, MA 02215, USA
    J Basic Clin Physiol Pharmacol 9:89-109. 1998
    ..Hopefully, these new techniques and new perspectives will bring us closer to understanding the pathophysiology of type 2 diabetes mellitus...
  29. ncbi request reprint Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle
    M E Patti
    Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    Diabetes 48:1562-71. 1999
    ....
  30. ncbi request reprint Overexpression of Rad inhibits glucose uptake in cultured muscle and fat cells
    J S Moyers
    Research Division, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 271:23111-6. 1996
    ..These data indicate that Rad is a negative regulator of glucose uptake and that this effect may be due to a decrease in the intrinsic activity of the transporter molecules, rather than an effect on the translocation of Glut4...
  31. pmc Insulin-stimulated translocation of GLUT4 glucose transporters requires SNARE-complex proteins
    B Cheatham
    Research Division, Joslin Diabetes Center, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 93:15169-73. 1996
    ....
  32. ncbi request reprint Insulin receptor substrate proteins create a link between the tyrosine phosphorylation cascade and the Ca2+-ATPases in muscle and heart
    P Algenstaedt
    Research Division, Joslin Diabetes Center and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 272:23696-702. 1997
    ....
  33. ncbi request reprint An association between NIDDM and a GAA trinucleotide repeat polymorphism in the X25/frataxin (Friedreich's ataxia) gene
    M Ristow
    Klinik II und Poliklinik für Innere Medizin, Universitat zu Koln, Cologne, Germany
    Diabetes 47:851-4. 1998
    ..Further studies are needed to elucidate the possible role of frataxin in the pathogenesis of NIDDM...
  34. ncbi request reprint Alterations in skeletal muscle gene expression of ob/ob mice by mRNA differential display
    D Vicent
    Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Diabetes 47:1451-8. 1998
    ....
  35. ncbi request reprint Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
    X J Sun
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215
    Nature 352:73-7. 1991
    ..Thus IRS-1 may link the insulin receptor kinase and enzymes regulating cellular growth and metabolism...
  36. ncbi request reprint Purification and partial sequence analysis of pp185, the major cellular substrate of the insulin receptor tyrosine kinase
    P L Rothenberg
    Research Division, Joslin Diabetes Center, Boston, Massachusetts
    J Biol Chem 266:8302-11. 1991
    ....
  37. ncbi request reprint 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...
  38. ncbi request reprint Obesity associated with a mutation in a genetic regulator of adipocyte differentiation
    M Ristow
    Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215, USA
    N Engl J Med 339:953-9. 1998
    ..Peroxisome-proliferator-activated receptor gamma2 (PPARgamma2) is a transcription factor that has a key role in adipocyte differentiation, and therefore mutations of the gene for this factor might predispose people to obesity...
  39. ncbi request reprint Human skeletal muscle insulin receptor substrate-1. Characterization of the cDNA, gene, and chromosomal localization
    E Araki
    Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts
    Diabetes 42:1041-54. 1993
    ..Thus, IRS-1 is widely expressed and highly conserved across species and tissues.(ABSTRACT TRUNCATED AT 250 WORDS)..
  40. pmc Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain
    D A Antonetti
    Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Cell Biol 16:2195-203. 1996
    ....
  41. ncbi request reprint Mutation of the insulin receptor at tyrosine 960 inhibits signal transmission but does not affect its tyrosine kinase activity
    M F White
    Joslin Diabetes Center, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02215
    Cell 54:641-9. 1988
    ....
  42. ncbi request reprint Vanadate normalizes hyperglycemia and phosphoenolpyruvate carboxykinase mRNA levels in ob/ob mice
    S Ferber
    Research Division, Joslin Diabetes Center, Boston, MA 02215
    Metabolism 43:1346-54. 1994
    ..In summary, hyperglycemia in the ob/ob mouse is characterized by decreased expression of PEPCK and increased expression of GAPDH mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)..
  43. pmc Unbalanced expression of the different subunits of elongation factor 1 in diabetic skeletal muscle
    C Reynet
    Research Division, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 98:3422-7. 2001
    ..This unbalanced regulation of the expression of the different subunits of EF-1 may contribute to alterations not only in protein synthesis but also in other cellular events observed in the diabetic state...
  44. ncbi request reprint Rad: a member of the Ras family overexpressed in muscle of type II diabetic humans
    C Reynet
    Research Division, Joslin Diabetes Center, Boston, MA
    Science 262:1441-4. 1993
    ..Messenger ribonucleic acid of Rad was expressed primarily in skeletal and cardiac muscle and was increased an average of 8.6-fold in the muscle of Type II diabetics as compared to normal individuals...
  45. ncbi request reprint Characterization of Rad, a new member of Ras/GTPase superfamily, and its regulation by a unique GTPase-activating protein (GAP)-like activity
    J Zhu
    Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215
    J Biol Chem 270:4805-12. 1995
    ..Rad may also be phosphorylated on serine/threonine residues by PKA and other kinases, as well as regulated by its own GAP which is present in many tissues and cell types...
  46. pmc Frataxin activates mitochondrial energy conversion and oxidative phosphorylation
    M Ristow
    Joslin Diabetes Center, Harvard Medical School, Research Division, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 97:12239-43. 2000
    ..Thus, frataxin appears to be a key activator of mitochondrial energy conversion and oxidative phosphorylation...
  47. pmc Interaction of the Ras-related protein associated with diabetes rad and the putative tumor metastasis suppressor NM23 provides a novel mechanism of GTPase regulation
    J Zhu
    Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 96:14911-8. 1999
    ..This interaction may play important roles in the effects of Rad on glucose metabolism and the effects of nm23 on tumor metastasis and developmental regulation...
  48. ncbi request reprint Trinucleotide repeats at the rad locus. Allele distributions in NIDDM and mapping to a 3-cM region on chromosome 16q
    A Doria
    Research Division, Joslin Diabetes Center, Boston, MA 02215
    Diabetes 44:243-7. 1995
    ..84 at recombination fractions of 0.024, 0.001, and 0.03, respectively). The high degree of heterozygosity of these markers will allow large-scale family studies to be performed to test the presence of linkage between rad and NIDDM...
  49. ncbi request reprint The role of insulin and IGF-1 signaling in longevity
    M Katic
    Joslin Diabetes Center and Department of Medicine Harvard Medical School, Boston, Massachusetts 02215, USA
    Cell Mol Life Sci 62:320-43. 2005
    ..These latter factors interact with each other, the former factors and histone deacetylases of the SIR family in a complex interaction to influence lifespan...
  50. pmc Effects of phosphorylation on function of the Rad GTPase
    J S Moyers
    Research Division, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA
    Biochem J 333:609-14. 1998
    ..These findings suggest that the binding of Rad to calmodulin, as well as its ability to bind GTP, might be regulated by the activation of several serine kinases...
  51. ncbi request reprint Rad and Rad-related GTPases interact with calmodulin and calmodulin-dependent protein kinase II
    J S Moyers
    Research Division, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 272:11832-9. 1997
    ..Thus, the Rad family of GTP-binding proteins possess unique characteristics of binding CaM and calmodulin-dependent protein kinase II, suggesting a role for Rad-like GTPases in calcium activation of serine/threonine kinase cascades...
  52. ncbi request reprint Cloning of the mouse insulin receptor substrate-1 (IRS-1) gene and complete sequence of mouse IRS-1
    E Araki
    Department of Medicine, Brigham and Women s Hospital, Boston, MA 02215
    Biochim Biophys Acta 1221:353-6. 1994
    ..The highly conserved nature of IRS-1 suggests the importance of these domains in the function of IRS-1 or its association with other proteins...
  53. ncbi request reprint Rad, a novel Ras-related GTPase, interacts with skeletal muscle beta-tropomyosin
    J Zhu
    Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
    J Biol Chem 271:768-73. 1996
    ..These data suggest that Rad may be involved in skeletal muscle motor function and cytoskeletal organization...
  54. ncbi request reprint Characterization and regulation of the mouse insulin receptor substrate gene promoter
    E Araki
    Joslin Diabetes Center, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Endocrinol 9:1367-79. 1995
    ....
  55. ncbi request reprint Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome
    Sudha B Biddinger
    Research Division, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Diabetes 54:1314-23. 2005
    ..Thus, dietary fat and genetic background act through SREBP-1c and SCD1 to affect hepatic lipid metabolism contributing to the development of the metabolic syndrome...
  56. pmc Evidence for a role of developmental genes in the origin of obesity and body fat distribution
    Stephane Gesta
    Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 103:6676-81. 2006
    ....
  57. ncbi request reprint Total insulin and IGF-I resistance in pancreatic beta cells causes overt diabetes
    Kohjiro Ueki
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nat Genet 38:583-8. 2006
    ..We propose that therapeutic improvement of insulin and IGF-I signaling in beta cells might protect against type 2 diabetes...
  58. ncbi request reprint Role of hepatic STAT3 in brain-insulin action on hepatic glucose production
    Hiroshi Inoue
    Department of Clinical Molecular Medicine, Division of Diabetes and Digestive and Kidney Diseases, Kobe University Graduate School of Medicine, Kobe 650 0017, Japan
    Cell Metab 3:267-75. 2006
    ..These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production...
  59. ncbi request reprint Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis
    Julia Baumgartl
    Institute for Genetics, University of Cologne and Center of Molecular Medicine Cologne, D 50931 Cologne, Germany
    Cell Metab 3:247-56. 2006
    ....
  60. pmc Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level
    Jacob Ilany
    Research Division, Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 103:4481-6. 2006
    ..These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes...
  61. pmc Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage
    Claude Knauf
    UMR 5018, Universite Paul Sabatier, IFR31, Toulouse, France USA
    J Clin Invest 115:3554-63. 2005
    ..Our data show that during hyperglycemia, brain GLP-1 inhibited muscle glucose utilization and increased insulin secretion to favor hepatic glycogen stores, preparing efficiently for the next fasting state...
  62. ncbi request reprint Increased P85alpha is a potent negative regulator of skeletal muscle insulin signaling and induces in vivo insulin resistance associated with growth hormone excess
    Linda A Barbour
    Department of Medicine, University Colorado Health Sciences Center, Denver, 80262, USA
    J Biol Chem 280:37489-94. 2005
    ....
  63. ncbi request reprint Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes
    Jenny E Gunton
    Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, Massachusetts 02215, USA
    Cell 122:337-49. 2005
    ..Together, these data suggest an important role for decreased ARNT and altered gene expression in the impaired islet function of human type 2 diabetes...
  64. ncbi request reprint Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin
    Yu Hua Tseng
    Research Division, Joslin Diabetes Center, Children s Hospital, Harvard Medical School, Boston, MA 02215, USA
    Nat Cell Biol 7:601-11. 2005
    ..Together these define a key signalling network that is involved in brown preadipocyte determination...
  65. ncbi request reprint Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and PKClambda/zeta
    Cullen M Taniguchi
    Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    Cell Metab 3:343-53. 2006
    ....
  66. ncbi request reprint Leptin suppresses stearoyl-CoA desaturase 1 by mechanisms independent of insulin and sterol regulatory element-binding protein-1c
    Sudha B Biddinger
    Research Division, Joslin Diabetes Center, One Joslin Pl, Boston, MA 02215, USA
    Diabetes 55:2032-41. 2006
    ..Thus, the effect of leptin on SCD1 in liver is independent of insulin and SREBP-1c, and leptin, rather than insulin, is the major regulator of hepatic MUFA synthesis in obesity-linked diabetes...
  67. pmc Beneficial effects of subcutaneous fat transplantation on metabolism
    Thien T Tran
    Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215, USA
    Cell Metab 7:410-20. 2008
    ..These data suggest that SC fat is intrinsically different from VIS fat and produces substances that can act systemically to improve glucose metabolism...
  68. pmc Central insulin action regulates peripheral glucose and fat metabolism in mice
    Linda Koch
    Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, and Center of Molecular Medicine Cologne, Cologne, Germany
    J Clin Invest 118:2132-47. 2008
    ..These studies demonstrate that central insulin action plays an important role in regulating WAT mass and glucose metabolism via hepatic Stat3 activation...
  69. pmc Impaired sodium excretion and increased blood pressure in mice with targeted deletion of renal epithelial insulin receptor
    Swasti Tiwari
    Department of Medicine, Georgetown University, Washington, DC 20057, USA
    Proc Natl Acad Sci U S A 105:6469-74. 2008
    ..These results illuminate a previously uncharacterized role for renal IR to reduce BP and facilitate sodium and water excretion, possibly via NO production...
  70. ncbi request reprint Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat-specific insulin receptor knock-out mice
    Masa Katic
    Joslin Diabetes Center, One Joslin Place and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Aging Cell 6:827-39. 2007
    ..Together, these data suggest that maintenance of mitochondrial activity and metabolic rates in adipose tissue may be important contributors to the increased lifespan of the FIRKO mouse...
  71. ncbi request reprint Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes
    J Andrew Pospisilik
    Institute of Molecular Biotechnology of the Austrian Academy of Science, Dr Bohrgasse 3, 1030, Vienna, Austria
    Cell 131:476-91. 2007
    ..These findings establish that tissue-specific as well as global OxPhos defects in mice can counteract the development of insulin resistance, diabetes, and obesity...
  72. ncbi request reprint IRS-1 transgenic mice show increased epididymal fat mass and insulin resistance
    Yusuke Murata
    Department of Metabolic Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 1 1 1 Honjo, Kumamoto 860 8556, Japan
    Biochem Biophys Res Commun 364:301-7. 2007
    ..Our results suggest that excess IRS-1 expression may not provide a beneficial impact on glucose homeostasis in vivo...
  73. pmc Muscle-specific knockout of PKC-lambda impairs glucose transport and induces metabolic and diabetic syndromes
    Robert V Farese
    James A Haley Veterans Medical Center, Tampa, Florida 33612, USA
    J Clin Invest 117:2289-301. 2007
    ..These findings are particularly relevant because humans who have obesity, impaired glucose tolerance, and T2DM reportedly have defective activation and/or diminished levels of muscle aPKC...
  74. ncbi request reprint High circulating leptin receptors with normal leptin sensitivity in liver-specific insulin receptor knock-out (LIRKO) mice
    Shmuel E Cohen
    Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    J Biol Chem 282:23672-8. 2007
    ..In this manner, insulin signaling in liver plays an important role in leptin homeostasis and fine modulation of leptin action...
  75. ncbi request reprint Reduced expression of the NADPH oxidase NOX4 is a hallmark of adipocyte differentiation
    Sarah Mouche
    Department of Cellular Physiology and Metabolism, University of Geneva, Geneva, Switzerland
    Biochim Biophys Acta 1773:1015-27. 2007
    ..In conclusion, we reveal that decreased NOX4 mRNA content is a hallmark of adipocyte differentiation and that NOX4 expression measured in whole adipose tissue is not an unequivocal indicator of intact or impaired insulin action...
  76. ncbi request reprint Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production
    A Christine Könner
    Department of Mouse Genetics and Metabolism, Institute for Genetics, Center for Molecular Medicine, University of Cologne, D 50674 Cologne, Germany
    Cell Metab 5:438-49. 2007
    ..However, insulin action specifically in AgRP-expressing neurons does play a critical role in controlling hepatic glucose production and may provide a target for the treatment of insulin resistance in type 2 diabetes...
  77. ncbi request reprint Protein-tyrosine phosphatase 1B deficiency reduces insulin resistance and the diabetic phenotype in mice with polygenic insulin resistance
    Bingzhong Xue
    Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Biol Chem 282:23829-40. 2007
    ..Thus, even in the setting of high genetic risk for diabetes, reducing PTP1B is partially protective, further demonstrating its attractiveness as a target for prevention and treatment of type 2 diabetes...
  78. pmc The p85alpha regulatory subunit of phosphoinositide 3-kinase potentiates c-Jun N-terminal kinase-mediated insulin resistance
    Cullen M Taniguchi
    Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Mol Cell Biol 27:2830-40. 2007
    ..Thus, p85alpha plays a dual role in regulating insulin sensitivity and may mediate cross talk between the PI3K and stress kinase pathways...
  79. pmc Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3
    Ho Jin Koh
    Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Mol Cell Biol 26:8217-27. 2006
    ..LKB1-mediated TRB3 expression provides a novel link between LKB1 and Akt, critical kinases involved in both tumor genesis and cell metabolism...
  80. pmc Suppression of aging in mice by the hormone Klotho
    Hiroshi Kurosu
    Department of Pathology, University of Texas UT Southwestern Medical Center at Dallas, 5323 Harry Hines Bouleuvard, Dallas, TX 75390 9072, USA
    Science 309:1829-33. 2005
    ..Klotho protein may function as an anti-aging hormone in mammals...
  81. pmc Muscle-specific Pten deletion protects against insulin resistance and diabetes
    Nadeeja Wijesekara
    Programme in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 2N9
    Mol Cell Biol 25:1135-45. 2005
    ..Muscle Pten may be a potential target for treatment or prevention of insulin resistance and diabetes...
  82. pmc Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization
    Tatsuya Kondo
    Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 111:1835-42. 2003
    ..These data indicate that both insulin and IGF-1 signaling in endothelium play a role in retinal neovascularization through the expression of vascular mediators, with the effect of insulin being most important in this process...
  83. ncbi request reprint Bi-directional regulation of brown fat adipogenesis by the insulin receptor
    Amelia J Entingh
    Department of Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, Massachusetts 02215, USA
    J Biol Chem 278:33377-83. 2003
    ..Thus, differentiation of brown adipocytes requires a timed and regulated expression of IR, and either the absence or overabundance of insulin receptors in these cells dramatically inhibits differentiation...
  84. ncbi request reprint Tissue-specific ablation of the GLUT4 glucose transporter or the insulin receptor challenges assumptions about insulin action and glucose homeostasis
    Yasuhiko Minokoshi
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 278:33609-12. 2003
  85. ncbi request reprint Impact of genetic background on development of hyperinsulinemia and diabetes in insulin receptor/insulin receptor substrate-1 double heterozygous mice
    Rohit N Kulkarni
    Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Diabetes 52:1528-34. 2003
    ....
  86. pmc GLUT4, AMP kinase, but not the insulin receptor, are required for hepatoportal glucose sensor-stimulated muscle glucose utilization
    Remy Burcelin
    Institute of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland
    J Clin Invest 111:1555-62. 2003
    ..These data demonstrate that the portal sensor induces glucose use and development of hypoglycemia independently of insulin action, but by a mechanism that requires activation of the AMPK and the presence of GLUT4...
  87. pmc The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance
    David Vicent
    Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 111:1373-80. 2003
    ....
  88. pmc Insulin signaling is required for insulin's direct and indirect action on hepatic glucose production
    Simon J Fisher
    Research Division, Joslin Diabetes Center, Harvard Medical School, Boston Massachusetts 02215, USA
    J Clin Invest 111:463-8. 2003
    ....
  89. ncbi request reprint Extended longevity in mice lacking the insulin receptor in adipose tissue
    Matthias Bluher
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA, 02215 USA
    Science 299:572-4. 2003
    ..Thus, a reduction of fat mass without caloric restriction can be associated with increased longevity in mice, possibly through effects on insulin signaling...
  90. ncbi request reprint Insulin-induced up-regulated uncoupling protein-1 expression is mediated by insulin receptor substrate 1 through the phosphatidylinositol 3-kinase/Akt signaling pathway in fetal brown adipocytes
    Angela M Valverde
    Departamento de Bioquimica y Biologia Molecular, Centro Mixto Consejo Superior de Investigaciones Cientificas Universidad Complutense de Madrid, Facultad de Farmacia, Universidad Complutense, Spain
    J Biol Chem 278:10221-31. 2003
    ..These data provide strong evidence for an essential role of IRS-1 through the PI 3-kinase/Akt signaling pathway inducing UCP-1 gene expression by insulin...
  91. pmc Lipoatrophic diabetes in Irs1(-/-)/Irs3(-/-) double knockout mice
    Palle G Laustsen
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Genes Dev 16:3213-22. 2002
    ..The results indicate that IRS-1 and IRS-3 play important complementary roles in adipogenesis and establish the Irs1(-/-)/Irs3(-/-) double knockout mouse as a novel model of lipoatrophic diabetes...
  92. ncbi request reprint Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance
    Matthias Bluher
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Dev Cell 3:25-38. 2002
    ....
  93. ncbi request reprint Knockout models are useful tools to dissect the pathophysiology and genetics of insulin resistance
    Franck Mauvais-Jarvis
    Department of Endocrinology and Diabetes, Saint Louis Hospital and University of Paris VII Medical School, France
    Clin Endocrinol (Oxf) 57:1-9. 2002
    ..The development of type 2 diabetes is linked to insulin resistance coupled with a failure of pancreatic beta-cells to compensate by adequate insulin secretion...
  94. ncbi request reprint Atypical beta-adrenergic effects on insulin signaling and action in beta(3)-adrenoceptor-deficient brown adipocytes
    Petra Jost
    Department of Internal Medicine I, Medical University of Lubeck, 23538 Lubeck, Germany
    Am J Physiol Endocrinol Metab 283:E146-53. 2002
    ..Furthermore, it indicates insulin receptor-independent, but PI 3-kinase-dependent, potent negative effects of the novel beta(1)-adrenoceptor state on diverse biological end points of insulin action...
  95. pmc Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression
    Darrell D Belke
    Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada
    J Clin Invest 109:629-39. 2002
    ..Insulin may also modulate cardiac myocyte metabolism through paracrine mechanisms by activating insulin receptors in other cell types within the heart...
  96. pmc Role of Foxa-2 in adipocyte metabolism and differentiation
    Christian Wolfrum
    Laboratory of Metabolic Diseases, The Rockefeller University, New York, New York 10021, USA
    J Clin Invest 112:345-56. 2003
    ..Furthermore, adipocytes of these Foxa-2+/- mice exhibit defects in glucose uptake and metabolism. These data suggest that Foxa-2 plays an important role as a physiological regulator of adipocyte differentiation and metabolism...
  97. pmc Muscle-specific PPARgamma-deficient mice develop increased adiposity and insulin resistance but respond to thiazolidinediones
    Andrew W Norris
    Research Division, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA
    J Clin Invest 112:608-18. 2003
    ..The tissue crosstalk mediating these effects is perhaps due to altered lipid metabolism in muscle...
  98. ncbi request reprint Genetic determinants of energy expenditure and insulin resistance in diet-induced obesity in mice
    Katrine Almind
    Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    Diabetes 53:3274-85. 2004
    ..e., the "thrifty gene," is a dominant-acting genetic determinant of diet-induced obesity in mice and can be linked to a locus on chromosome 14, including genes linked to adipose development and insulin sensitivity...
  99. pmc Distinct pathways of insulin-regulated versus diabetes-regulated gene expression: an in vivo analysis in MIRKO mice
    Vijay K Yechoor
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 101:16525-30. 2004
    ..These distinct pathways of direct and indirect regulation of gene expression provide insights into the complex mechanisms of transcriptional control in diabetes and areas of potential therapeutic targeting...
  100. pmc Loss of skeletal muscle HIF-1alpha results in altered exercise endurance
    Steven D Mason
    Molecular Biology Section, Division of Biology, School of Medicine, University of California, San Diego, USA
    PLoS Biol 2:e288. 2004
    ..Thus, these results demonstrate an important role for the HIF-1 pathway in the metabolic control of muscle function...
  101. pmc Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse
    Kohjiro Ueki
    Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 101:10422-7. 2004
    ..Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling...

Research Grants60

  1. Developmental Genes and the Origin of Fat
    C Ronald Kahn; Fiscal Year: 2010
    ....
  2. PI 3 KINASE ISOFORMS AND INSULIN ACTION
    C Kahn; Fiscal Year: 2003
    ..Together these studies should provide important insights into the role of PI 3-kinase isoforms in insulin action and diabetes. ..
  3. GENE EXPRESSION IN DIABETES BY SUBTRACTIVE CLONING
    C Kahn; Fiscal Year: 2003
    ..In addition, 6 type 2 DM having low S1 and SG on fs-IVGTT will be compared with 6 offspring with high S1 and high SG, and 6 normoglycemic obese will be compared with 6 lean subjects, for differential expression in muscle and fat. ..
  4. PI 3-Kinase Isoforms and Insulin Action
    C Kahn; Fiscal Year: 2006
    ..abstract_text> ..
  5. PI 3-Kinase Isoforms in Insulin Action
    C Ronald Kahn; Fiscal Year: 2010
    ....
  6. Insulin Receptor Substrates and Insulin Action
    C Ronald Kahn; Fiscal Year: 2010
    ....
  7. Developmental Genes and the Origin of Fat
    C Ronald Kahn; Fiscal Year: 2010
    ....
  8. PI 3-Kinase Isoforms in Insulin Action
    C Kahn; Fiscal Year: 2009
    ....
  9. Developmental Genes and the Origin of Fat
    C Kahn; Fiscal Year: 2009
    ....
  10. PI 3-Kinase Isoforms in Insulin Action
    C Kahn; Fiscal Year: 2007
    ....
  11. Insulin Receptor Substrates and Insulin Action
    C Kahn; Fiscal Year: 2007
    ..Identify the chromosomal loci and the specific genes in these loci which modify insulin resistance in the double heterozygous mouse leading to marked differences in diabetic phenotype in C57B1 and 129Sv mice. ..
  12. INSULIN RECEPTOR STRUCTURE AND TURNOVER
    C Kahn; Fiscal Year: 2007
    ..4) Analyze gene expression in tissues lacking functional insulin receptors to define differences in direct and indirect regulation by insulin and metabolic substrates in this class of insulin actions. ..
  13. Diabetes Genome Anatomy Project (DGAP)
    C Kahn; Fiscal Year: 2006
    ..abstract_text> ..
  14. INSULIN RECEPTOR PHOSPHORYLATION AND INSULIN ACTION
    C Kahn; Fiscal Year: 2002
    ..Together these studies should provide important insights into the complex network of insulin signaling and its alternations in diabetes. ..
  15. CONFERENCE ON DIABETES MELLITUS
    C Kahn; Fiscal Year: 2002
    ..Keystone conferences on diabetes have been held every 2-3 years, and have had increasing registration approaching 600 people (when combined with the obesity conference). ..
  16. CHANGES IN GENE EXPRESSION IN DIABETES
    C Kahn; Fiscal Year: 1999
    ....
  17. GENE EXPRESSION IN DIABETES BY SUBTRACTIVE CLONING
    C Kahn; Fiscal Year: 2000
    ..abstract_text> ..
  18. CHANGES IN GENE EXPRESSION IN DIABETES
    C Kahn; Fiscal Year: 1993
    ....
  19. INSULIN RECEPTOR PHOSPHORYLATION AND INSULIN ACTION
    C Kahn; Fiscal Year: 1993
    ..7. Disease and cell culture models of altered receptor kinase activity will be further studied to determine the exact mechanism responsible for the change...