Gerald Shulman

Summary

Affiliation: Yale University
Country: USA

Publications

  1. ncbi Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance
    Jie An
    Sarah W. Stedman Nutrition and Metabolism Center and Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nat Med 10:268-74. 2004
  2. ncbi Cellular mechanism by which estradiol protects female ovariectomized mice from high-fat diet-induced hepatic and muscle insulin resistance
    Joao Paulo G Camporez
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536 9812, USA
    Endocrinology 154:1021-8. 2013
  3. ncbi Regulation of mitochondrial biogenesis by lipoprotein lipase in muscle of insulin-resistant offspring of parents with type 2 diabetes
    Katsutaro Morino
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA
    Diabetes 61:877-87. 2012
  4. ncbi Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis
    Richard M Reznick
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell Metab 5:151-6. 2007
  5. ncbi Unraveling the cellular mechanism of insulin resistance in humans: new insights from magnetic resonance spectroscopy
    Gerald I Shulman
    Departments of Internal Medicine and Cellular and Molecular Physiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Physiology (Bethesda) 19:183-90. 2004
  6. ncbi Thyroid hormone receptor-α gene knockout mice are protected from diet-induced hepatic insulin resistance
    Francois R Jornayvaz
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    Endocrinology 153:583-91. 2012
  7. ncbi SirT1 regulates adipose tissue inflammation
    Matthew P Gillum
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA
    Diabetes 60:3235-45. 2011
  8. ncbi Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction
    Katsutaro Morino
    Howard Hughes Medical Institute, Yale University School of Medicine, P O Box 9812, New Haven, CT 06536 8012, USA
    Diabetes 55:S9-S15. 2006
  9. ncbi Effect of AMPK activation on muscle glucose metabolism in conscious rats
    R Bergeron
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8020, USA
    Am J Physiol 276:E938-44. 1999
  10. ncbi Effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats
    R Bergeron
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Diabetes 50:1076-82. 2001

Research Grants

  1. IN VIVO NMR STUDIES OF CARBOHYDRATE METABOLISM
    Gerald Shulman; Fiscal Year: 2002
  2. Mechanisms of Fatty Acid Induced Insulin Resistance
    Gerald Shulman; Fiscal Year: 2003
  3. CELLULAR MECHANISMS OF INSULIN RESISTANCE IN HUMANS
    Gerald Shulman; Fiscal Year: 2004
  4. Yale Mouse Metabolic Phenotyping Center
    Gerald Shulman; Fiscal Year: 2005
  5. Mechanisms of Fatty Acid Induced Insulin Resistance
    Gerald Shulman; Fiscal Year: 2006
  6. Mechanisms of Fat Induced Insulin Resistance
    Gerald Shulman; Fiscal Year: 2007
  7. Mechanisms of Fat Induced Insulin Resistance
    Gerald I Shulman; Fiscal Year: 2010
  8. NMR STUDIES OF GLYCOGEN METABOLISM IN HUMANS
    Gerald Shulman; Fiscal Year: 1999
  9. IN VIVO NMR STUDIES OF CARBOHYDRATE METABOLISM
    Gerald Shulman; Fiscal Year: 1993
  10. CELLULAR MECHANISMS OF INSULIN RESISTANCE IN HUMANS
    Gerald I Shulman; Fiscal Year: 2010

Detail Information

Publications95

  1. ncbi Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance
    Jie An
    Sarah W. Stedman Nutrition and Metabolism Center and Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nat Med 10:268-74. 2004
    ..The best explanation for our findings is that hepatic expression of MCD lowered circulating FFA levels, which led to lowering of muscle beta-OH-butyrate levels and improvement of insulin sensitivity...
  2. ncbi Cellular mechanism by which estradiol protects female ovariectomized mice from high-fat diet-induced hepatic and muscle insulin resistance
    Joao Paulo G Camporez
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536 9812, USA
    Endocrinology 154:1021-8. 2013
    ....
  3. ncbi Regulation of mitochondrial biogenesis by lipoprotein lipase in muscle of insulin-resistant offspring of parents with type 2 diabetes
    Katsutaro Morino
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA
    Diabetes 61:877-87. 2012
    ..Taken together, these data suggest that decreased mitochondrial content in muscle of IR offspring may be due in part to reductions in LPL expression in skeletal muscle resulting in decreased PPAR-δ activation...
  4. ncbi Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis
    Richard M Reznick
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell Metab 5:151-6. 2007
    ..These results suggest that aging-associated reductions in AMPK activity may be an important contributing factor in the reduced mitochondrial function and dysregulated intracellular lipid metabolism associated with aging...
  5. ncbi Unraveling the cellular mechanism of insulin resistance in humans: new insights from magnetic resonance spectroscopy
    Gerald I Shulman
    Departments of Internal Medicine and Cellular and Molecular Physiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Physiology (Bethesda) 19:183-90. 2004
    ..In this review, some recent advances in the understanding of insulin resistance in humans that have been made by using magnetic resonance spectroscopy are discussed...
  6. ncbi Thyroid hormone receptor-α gene knockout mice are protected from diet-induced hepatic insulin resistance
    Francois R Jornayvaz
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    Endocrinology 153:583-91. 2012
    ..Therefore, thyroid receptor-α inhibition represents a novel pharmacologic target for the treatment of NAFLD, obesity, and type 2 diabetes...
  7. ncbi SirT1 regulates adipose tissue inflammation
    Matthew P Gillum
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA
    Diabetes 60:3235-45. 2011
    ..We discovered that SirT1 depletion causes anorexia by stimulating production of inflammatory factors in white adipose tissue and thus posit that decreases in SirT1 link overnutrition and adipose tissue inflammation...
  8. ncbi Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction
    Katsutaro Morino
    Howard Hughes Medical Institute, Yale University School of Medicine, P O Box 9812, New Haven, CT 06536 8012, USA
    Diabetes 55:S9-S15. 2006
    ..By elucidating the cellular and molecular mechanisms responsible for insulin resistance, these studies provide potential new targets for the treatment and prevention of type 2 diabetes...
  9. ncbi Effect of AMPK activation on muscle glucose metabolism in conscious rats
    R Bergeron
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8020, USA
    Am J Physiol 276:E938-44. 1999
    ..In conclusion, the activation of AMPK by AICAR increases skeletal muscle glucose transport activity both in vivo and in vitro. This cellular pathway may play an important role in exercise-induced increase in glucose transport activity...
  10. ncbi Effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats
    R Bergeron
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Diabetes 50:1076-82. 2001
    ....
  11. ncbi Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance
    J K Kim
    Howard Hughes Medical Institute and Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 98:7522-7. 2001
    ....
  12. ncbi Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle
    J K Kim
    Department of Internal Medicine and the Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA
    J Clin Invest 105:1791-7. 2000
    ..These data demonstrate that selective insulin resistance in muscle promotes redistribution of substrates to adipose tissue thereby contributing to increased adiposity and development of the prediabetic syndrome...
  13. ncbi Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4
    J K Kim
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536 8012, USA
    J Clin Invest 108:153-60. 2001
    ..These secondary defects contribute to insulin resistance and to the development of diabetes...
  14. ncbi Contribution of net hepatic glycogen synthesis to disposal of an oral glucose load in humans
    K F Petersen
    Department of Internal Medicine and the Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA
    Metabolism 50:598-601. 2001
    ..In conclusion, after ingestion of 98 g of glucose: (1) 16.7 +/- 3.8 g (17% +/- 4%) glucose was stored in the liver as glycogen, and (2) 63% +/- 7% (10.5 +/- 2.4 g) of this glycogen was formed via the direct pathway...
  15. ncbi Transgenic mice overexpressing GLUT-1 protein in muscle exhibit increased muscle glycogenesis after exercise
    J M Ren
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Am J Physiol Endocrinol Metab 278:E588-92. 2000
    ..Our data suggest that the high level of steady-state muscle glycogen in TG mice is due to the increase in muscle glucose transport activity...
  16. ncbi Prevention of fat-induced insulin resistance by salicylate
    J K Kim
    Howard Hughes Medical Institute, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06536-8012, USA
    J Clin Invest 108:437-46. 2001
    ....
  17. 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...
  18. ncbi AICAR and phlorizin reverse the hypoglycemia-specific defect in glucagon secretion in the diabetic BB rat
    R J McCrimmon
    Department of Internal Medicine and Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Am J Physiol Endocrinol Metab 283:E1076-83. 2002
    ..We conclude that alpha-cell glucagon secretion in response to hypoglycemia is not defective if intraislet hyperinsulinemia is prevented. This suggests that exogenous insulin plays a pivotal role in the etiology of this defect...
  19. ncbi Impaired insulin sensitivity among nondiabetic patients with a recent TIA or ischemic stroke
    W N Kernan
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 8025, USA
    Neurology 60:1447-51. 2003
    ..To determine the prevalence of impaired insulin sensitivity among nondiabetic patients with a recent TIA or nondisabling ischemic stroke...
  20. ncbi Metabolic control analysis of insulin-stimulated glucose disposal in rat skeletal muscle
    B M Jucker
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8020, USA
    Am J Physiol 277:E505-12. 1999
    ....
  21. ncbi Stimulating effects of low-dose fructose on insulin-stimulated hepatic glycogen synthesis in humans
    K F Petersen
    Department of Internal Medicine, Yale University School of Medicine, 333 Cedar St, FMP 104, New Haven, CT 06520 8020, USA
    Diabetes 50:1263-8. 2001
    ..Because net hepatic glycogen synthesis has been shown to be diminished in patients with poorly controlled type 1 and type 2 diabetes, stimulation of hepatic glycogen synthesis by this mechanism may be of potential therapeutic value...
  22. ncbi Preliminary evidence of low cortical GABA levels in localized 1H-MR spectra of alcohol-dependent and hepatic encephalopathy patients
    K L Behar
    Department of Neurology, Yale University, New Haven, CT 06520 8043, USA
    Am J Psychiatry 156:952-4. 1999
    ..The aim of the study was to compare levels of neuroactive amino acids in the cerebral cortex of healthy subjects, recently detoxified alcohol-dependent patients, and patients with hepatic encephalopathy...
  23. ncbi Mechanism of troglitazone action in type 2 diabetes
    K F Petersen
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8020, USA
    Diabetes 49:827-31. 2000
    ....
  24. ncbi Glycogen loading alters muscle glycogen resynthesis after exercise
    T B Price
    Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Appl Physiol 88:698-704. 2000
    ..001). We conclude that glycogen recovery from heavy exercise is controlled primarily by the remaining postexercise glycogen concentration, with only a transient synthesis period when glycogen levels are not severely reduced...
  25. ncbi Differential effects of safflower oil versus fish oil feeding on insulin-stimulated glycogen synthesis, glycolysis, and pyruvate dehydrogenase flux in skeletal muscle: a 13C nuclear magnetic resonance study
    B M Jucker
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8020, USA
    Diabetes 48:134-40. 1999
    ....
  26. ncbi Contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production in cirrhosis
    K F Petersen
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Conneticut 06520 8020, USA
    Am J Physiol 276:E529-35. 1999
    ..These alterations are likely important contributing factors to their altered carbohydrate metabolism...
  27. ncbi Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo
    L H Young
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 8017, USA
    Circulation 95:415-22. 1997
    ..Myocardial ischemia increases heart glucose utilization in vivo. However, whether low-flow ischemia leads to the translocation of glucose transporter (GLUT)-4 and/or GLUT-1 to the sarcolemma in vivo is unknown...
  28. ncbi Triiodothyronine treatment increases substrate cycling between pyruvate carboxylase and malic enzyme in perfused rat liver
    K F Petersen
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 8020, USA
    Metabolism 44:1380-3. 1995
    ..36 +/- 0.05 U/g liver in normal livers to 2.51 +/- 0.50 U/g liver (P < .05) in the T3-treated group, whereas there was no effect of T3 treatment on pyruvate kinase activity.(ABSTRACT TRUNCATED AT 250 WORDS)..
  29. ncbi 13C/31P NMR studies on the mechanism of insulin resistance in obesity
    K F Petersen
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8020, USA
    Diabetes 47:381-6. 1998
    ..We conclude that insulin resistance in obesity can be mostly attributed to impairment of insulin-stimulated muscle glycogen synthesis due to a defect in glucose transport and/or phosphorylation activity...
  30. ncbi Low adiponectin levels in adolescent obesity: a marker of increased intramyocellular lipid accumulation
    Ram Weiss
    Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    J Clin Endocrinol Metab 88:2014-8. 2003
    ..The putative modulatory effects of adiponectin on insulin sensitivity may, in part, be mediated via its effects on IMCL lipid content...
  31. ncbi Immunocytochemical localization of alpha-protein kinase C in rat pancreatic beta-cells during glucose-induced insulin secretion
    S Ganesan
    Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut
    J Cell Biol 119:313-24. 1992
    ....
  32. ncbi 13C/31P NMR assessment of mitochondrial energy coupling in skeletal muscle of awake fed and fasted rats. Relationship with uncoupling protein 3 expression
    B M Jucker
    Howard Hughes Medical Institute and the Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    J Biol Chem 275:39279-86. 2000
    ..Furthermore, UCP3 does not appear to have a major role in FFA translocation into the mitochondria. The physiological role of UCP3 following a 48-h fast in skeletal muscle remains to be elucidated...
  33. ncbi A critical evaluation of mass isotopomer distribution analysis of gluconeogenesis in vivo
    S F Previs
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8020, USA
    Am J Physiol 277:E154-60. 1999
    ....
  34. ncbi Substrate cycling between pyruvate and oxaloacetate in awake normal and 3,3'-5-triiodo-L-thyronine-treated rats
    K F Petersen
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8020
    Am J Physiol 267:E273-7. 1994
    ..47 +/- 0.15 vs. T3 treated 0.77 +/- 0.03, P < 0.05) and the activity of ME (normal 0.89 +/- 0.30 U/g liver vs. T3 treated 4.25 +/- 0.60 U/g liver, P < 0.05) increased with T3 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)..
  35. ncbi Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle
    V Lebon
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Clin Invest 108:733-7. 2001
    ..Given the disproportionate increase in TCA cycle flux compared with ATP synthesis, these data suggest that T(3) promotes increased thermogenesis in part by promoting mitochondrial energy uncoupling in skeletal muscle...
  36. ncbi Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis
    R Bergeron
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Am J Physiol Endocrinol Metab 281:E1340-6. 2001
    ..Our data suggest that AMPK may play an important role in muscle adaptations to chronic energy stress and that it promotes mitochondrial biogenesis and expression of respiratory proteins through activation of NRF-1...
  37. ncbi Lipid metabolism and adipokine levels in fatty acid-binding protein null and transgenic mice
    Ann V Hertzel
    Dept of Biochemistry, Molecular Biology, and Biophysics, Univ of Minnesota, 321 Church St SE, Minneapolis, MN 55455, USA
    Am J Physiol Endocrinol Metab 290:E814-23. 2006
    ....
  38. ncbi n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner
    Susanne Neschen
    Yale University School of Medicine, Howard Hughes Medical Institute, Departments of Internal Medicine, The Anlyan Center, P O Box 9812, New Haven, CT 06536 8012, USA
    Diabetes 56:1034-41. 2007
    ..0001 vs. genotype control). These data support the hypothesis that n-3 fatty acids protect from high-fat diet-induced hepatic insulin resistance in a PPAR-alpha-and diacylglycerol-dependent manner...
  39. ncbi Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals
    Qian Gao
    Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nat Med 13:89-94. 2007
    ....
  40. ncbi Hypomorphic mutation of PGC-1beta causes mitochondrial dysfunction and liver insulin resistance
    Claudia R Vianna
    Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Cell Metab 4:453-64. 2006
    ..Importantly, these abnormalities do not cause insulin resistance in skeletal muscle but cause substantially reduced insulin action in the liver...
  41. ncbi Urocortin 2 modulates glucose utilization and insulin sensitivity in skeletal muscle
    Alon Chen
    Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 103:16580-5. 2006
    ....
  42. ncbi Immunoneutralization of endogenous glucagon reduces hepatic glucose output and improves long-term glycemic control in diabetic ob/ob mice
    Heidi Sørensen
    Diabetes Research Unit, Novo Nordisk Park, 2760 Måløv, Denmark
    Diabetes 55:2843-8. 2006
    ..In conclusion, acute and subchronic neutralization of endogenous glucagon improves glycemic control, thus supporting the contention that glucagon antagonism may represent a beneficial treatment of diabetes...
  43. ncbi Mice lacking MAP kinase phosphatase-1 have enhanced MAP kinase activity and resistance to diet-induced obesity
    J Julie Wu
    Department of Pharmacology, Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Cell Metab 4:61-73. 2006
    ..These results suggest that nuclear regulation of the MAPKs by MKP-1 is essential for the management of metabolic homeostasis in a manner that is spatially uncoupled from the cytosolic actions of the MAPKs...
  44. ncbi Effect of a sustained reduction in plasma free fatty acid concentration on intramuscular long-chain fatty Acyl-CoAs and insulin action in type 2 diabetic patients
    Mandeep Bajaj
    Diabetes Division, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA
    Diabetes 54:3148-53. 2005
    ....
  45. ncbi Mechanism of glucose intolerance in mice with dominant negative mutation of CEACAM1
    So Young Park
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
    Am J Physiol Endocrinol Metab 291:E517-24. 2006
    ..Our findings further indicate the important role of CEACAM1 and hepatic insulin clearance in the pathogenesis of obesity and insulin resistance...
  46. ncbi Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents
    Katsutaro Morino
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536 8012, USA
    J Clin Invest 115:3587-93. 2005
    ....
  47. ncbi Etiology of insulin resistance
    Kitt Falk Petersen
    Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Am J Med 119:S10-6. 2006
    ..Understanding the cellular mechanism(s) of insulin resistance in turn offers the prospect of better targeted and more effective therapeutic interventions for treatment and prevention of type 2 diabetes...
  48. ncbi The SHP-1 protein tyrosine phosphatase negatively modulates glucose homeostasis
    Marie Julie Dubois
    Department of Anatomy Physiology and Lipid Research Unit, Laval University Hospital Research Center, 2705 Laurier Boulevard, Quebec, Quebec G1V 4G2, Canada
    Nat Med 12:549-56. 2006
    ..These findings show a novel role for SHP-1 in the regulation of glucose homeostasis through modulation of insulin signaling in liver and muscle as well as hepatic insulin clearance...
  49. ncbi Obesity-associated improvements in metabolic profile through expansion of adipose tissue
    Ja Young Kim
    Department of Cell Biology, Albert Einstein College of Medicine, New York, New York, USA
    J Clin Invest 117:2621-37. 2007
    ..These mice therefore represent what we believe is a novel model of morbid obesity associated with an improved metabolic profile...
  50. ncbi UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals
    Zane B Andrews
    Section of Comparative Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Howard Hughes Medical Institute, New York, New York 10021, USA
    Nature 454:846-51. 2008
    ..These results reveal a signalling modality connecting mitochondria-mediated effects of G-protein-coupled receptors on neuronal function and associated behaviour...
  51. ncbi Regulation of hypothalamic malonyl-CoA by central glucose and leptin
    Michael J Wolfgang
    Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 104:19285-90. 2007
    ..These studies show that hypothalamic malonyl-CoA responds to the level of circulating glucose and leptin, both of which affect energy homeostasis...
  52. ncbi Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance
    Dongyan Zhang
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 104:17075-80. 2007
    ..These data demonstrate that primary defects in mitochondrial fatty acid oxidation capacity can lead to diacylglycerol accumulation, PKCepsilon activation, and hepatic insulin resistance...
  53. ncbi Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk
    Christoph Handschin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 117:3463-74. 2007
    ..These data clearly illustrate a causal role for muscle PGC-1alpha in maintenance of glucose homeostasis and highlight an unexpected cytokine-mediated crosstalk between skeletal muscle and pancreatic islets...
  54. ncbi Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity
    Cheol Soo Choi
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 104:16480-5. 2007
    ..Taken together with previous work demonstrating that Acc2(-/-) mice have a normal lifespan, these data suggest that Acc2 inhibition is a viable therapeutic option for the treatment of obesity and type 2 diabetes...
  55. ncbi 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...
  56. ncbi Effects of rexinoids on glucose transport and insulin-mediated signaling in skeletal muscles of diabetic (db/db) mice
    Qi Shen
    Department of Integrative Biology and Pharmacology, University of Texas Medical School, 6431 Fannin Street, Houston, TX 77225, USA
    J Biol Chem 279:19721-31. 2004
    ..Rexinoids represent a novel class of insulin sensitizers with potential applications in the treatment of insulin resistance...
  57. ncbi Suppression of diacylglycerol acyltransferase-2 (DGAT2), but not DGAT1, with antisense oligonucleotides reverses diet-induced hepatic steatosis and insulin resistance
    Cheol Soo Choi
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 282:22678-88. 2007
    ....
  58. ncbi Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia
    Qingchun Tong
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA
    Cell Metab 5:383-93. 2007
    ..Thus, glutamate release from VMH neurons is an important component of the neurocircuitry that functions to prevent hypoglycemia...
  59. ncbi Disordered lipid metabolism and the pathogenesis of insulin resistance
    David B Savage
    Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536 8012, USA
    Physiol Rev 87:507-20. 2007
    ..in 2004, we will concentrate on human studies involving the use of isotopes and/or magnetic resonance spectroscopy, occasionally drawing on mouse models which provide additional mechanistic insight...
  60. ncbi Hepatic overexpression of glycerol-sn-3-phosphate acyltransferase 1 in rats causes insulin resistance
    Cynthia A Nagle
    Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 282:14807-15. 2007
    ..These results indicate that increased flux through the pathway of hepatic de novo triacylglycerol synthesis can cause hepatic and systemic insulin resistance in the absence of obesity or a lipogenic diet...
  61. ncbi Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo
    Jonathan B Hurov
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110 1093, USA
    Proc Natl Acad Sci U S A 104:5680-5. 2007
    ..Taken together, these data indicate that Par-1b is a regulator of glucose metabolism and adiposity in the whole animal and may be a valuable drug target for the treatment of both type 2 diabetes and obesity...
  62. ncbi Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients
    Douglas E Befroy
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06536 8012, USA
    Diabetes 56:1376-81. 2007
    ....
  63. ncbi Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance
    Cheol Soo Choi
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536 9812, USA
    J Clin Invest 117:1995-2003. 2007
    ..These results suggest that increasing mitochondrial uncoupling in skeletal muscle may be an excellent therapeutic target for type 2 diabetes mellitus...
  64. ncbi Decreased insulin-stimulated ATP synthesis and phosphate transport in muscle of insulin-resistant offspring of type 2 diabetic parents
    Kitt F Petersen
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
    PLoS Med 2:e233. 2005
    ..Furthermore, these IR offspring also have impaired insulin-stimulated phosphate transport in muscle, which may contribute to their defects in insulin-stimulated rates of mitochondrial ATP synthesis...
  65. ncbi Prevention of hepatic steatosis and hepatic insulin resistance in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice
    Susanne Neschen
    Howard Hughes Medical Institute, Department of Internal Medicine, Yale University School of Medicine, New Haven, CN 06520, USA
    Cell Metab 2:55-65. 2005
    ..These data suggest that mtGPAT1 might serve as a novel target for treatment of hepatic steatosis and hepatic insulin resistance and that long chain acyl-CoA's do not mediate fat-induced hepatic insulin resistance in this model...
  66. ncbi Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning
    Ram Weiss
    Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA
    Lancet 362:951-7. 2003
    ..INTERPRETATION: In obese children and adolescents with prediabetes, intramyocellular and intra-abdominal lipid accumulation is closely linked to the development of severe peripheral insulin resistance...
  67. ncbi Insulin resistance in tetracycline-repressible Munc18c transgenic mice
    Beth A Spurlin
    Department of Biochemistry and Molecular Biology, Center for Diabetes Research, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Diabetes 52:1910-7. 2003
    ..Taken together, these results indicate that balance, more than absolute abundance, of Munc18c and Syn4 proteins directly affects whole-body glucose homeostasis through alterations in insulin secretion and insulin action...
  68. ncbi Phosphoinositide profiling in complex lipid mixtures using electrospray ionization mass spectrometry
    Markus R Wenk
    Howard Hughes Medical Institute, Department of Cell Biology, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, Connecticut 06511, USA
    Nat Biotechnol 21:813-7. 2003
    ..Mass spectrometric analysis of phosphoinositides offers unique advantages over existing approaches and may represent a powerful diagnostic tool for human diseases that involve defective phosphoinositide metabolism...
  69. ncbi Mitochondrial dysfunction in the elderly: possible role in insulin resistance
    Kitt Falk Petersen
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
    Science 300:1140-2. 2003
    ..These data support the hypothesis that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly...
  70. ncbi Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy
    Kitt Falk Petersen
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8020, USA
    J Clin Invest 109:1345-50. 2002
    ..These data suggest that leptin may represent an important new therapy to reverse the severe hepatic and muscle insulin resistance and associated hepatic steatosis in patients with lipodystrophy...
  71. ncbi Defective activation of skeletal muscle and adipose tissue lipolysis in type 1 diabetes mellitus during hypoglycemia
    Staffan Enoksson
    Department of Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Clin Endocrinol Metab 88:1503-11. 2003
    ..This defect within peripheral tissues may lead to a delayed increase in glucose disposal that could contribute to the severity of hypoglycemia when it is prolonged...
  72. ncbi A comparison of (13)C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-(13)C]glucose
    Graeme F Mason
    Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
    Brain Res Brain Res Protoc 10:181-90. 2003
    ..The conclusion is that oral administration does yield the same result as intravenous administration but with lower precision. That sensitivity of the oral protocol may be improved by several ways that are available today...
  73. ncbi Pathogenesis of skeletal muscle insulin resistance in type 2 diabetes mellitus
    Kitt F Petersen
    Howard Hughes Medical Institute, Department of Internal Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA
    Am J Cardiol 90:11G-18G. 2002
    ....
  74. ncbi [2,4-13 C2 ]-beta-Hydroxybutyrate metabolism in human brain
    Jullie W Pan
    Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Cereb Blood Flow Metab 22:890-8. 2002
    ..6% of total acetyl coenzyme A oxidation. These results are consistent with minimal accumulation of cerebral ketones with rapid utilization, implying blood-brain barrier control of ketone oxidation in the nonfasted adult human brain...
  75. ncbi Fatty acid infusion selectively impairs insulin action on Akt1 and protein kinase C lambda /zeta but not on glycogen synthase kinase-3
    Young Bum Kim
    Diabetes Unit, Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 277:32915-22. 2002
    ....
  76. ncbi Adrenalectomy improves diabetes in A-ZIP/F-1 lipoatrophic mice by increasing both liver and muscle insulin sensitivity
    Martin Haluzik
    Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases NIH, Building 10, Room 8N 250, 10 Center Drive, Bethesda, MD 20892 1770, USA
    Diabetes 51:2113-8. 2002
    ..These results suggest that the chronically increased serum corticosterone levels contribute to the diabetes of the A-ZIP/F-1 mice and that removal of the glucocorticoid excess improves the insulin sensitivity in both muscle and liver...
  77. ncbi Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle
    Chunli Yu
    Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 277:50230-6. 2002
    ..This in turn leads to decreased IRS-1 tyrosine phosphorylation and decreased activation of IRS-1-associated PI3-kinase activity resulting in decreased insulin-stimulated glucose transport activity...
  78. ncbi Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism
    Vincent Lebon
    Howard Hughes Medical Institute, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Neurosci 22:1523-31. 2002
    ..The further application of this approach could potentially enlighten the role of astroglia in supporting brain glutamatergic activity and in neurological and psychiatric disease...
  79. ncbi The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes
    Adam B Mayerson
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA
    Diabetes 51:797-802. 2002
    ....
  80. ncbi Genetic modulation of PPARgamma phosphorylation regulates insulin sensitivity
    Shamina M Rangwala
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Dev Cell 5:657-63. 2003
    ..Compounds that prevent PPARgamma phosphorylation or ligands that induce the conformation of nonphosphorylated PPARgamma may selectively enhance insulin sensitivity without increasing body weight...
  81. ncbi Liver fatty acid binding protein is required for high rates of hepatic fatty acid oxidation but not for the action of PPARalpha in fasting mice
    Erdal Erol
    Department of Pathobiology, College of Veterinary Medicine, Texas A and M University, Raymond Stotzer Pkwy, College Station, Texas 77843 4467, USA
    FASEB J 18:347-9. 2004
    ..Thus, the mechanisms whereby L-FABP affects fatty acid oxidation may vary with physiological condition...
  82. ncbi The role of intramyocellular lipids during hypoglycemia in patients with intensively treated type 1 diabetes
    Elisabeth Bernroider
    Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Austria
    J Clin Endocrinol Metab 90:5559-65. 2005
    ..c. adipose tissue lipolysis...
  83. ncbi Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential in liver for the metabolism of excess acyl-CoAs
    Linda E Hammond
    Department of Nutrition, University of North Carolina, North Chapel Hill, Carolina 27599, USA
    J Biol Chem 280:25629-36. 2005
    ....
  84. ncbi Mechanisms of insulin resistance in humans and possible links with inflammation
    David B Savage
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn 06510, USA
    Hypertension 45:828-33. 2005
    ..Understanding the molecular/biochemical defects responsible for insulin resistance is beginning to unveil novel therapeutic targets for treatment of the metabolic syndrome and type 2 diabetes...
  85. ncbi The "obese insulin-sensitive" adolescent: importance of adiponectin and lipid partitioning
    Ram Weiss
    Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, P O Box 208064, New Haven, Connecticut 06520, USA
    J Clin Endocrinol Metab 90:3731-7. 2005
    ..Obese insulin-sensitive adolescents are characterized by lower lipid deposition in the intramyocellular and visceral compartments and greater levels of adiponectin, despite similar degree of adiposity...
  86. ncbi Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart
    So Young Park
    Department of Internal Medicine, Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, CT 06520 8020, USA
    Am J Physiol Endocrinol Metab 289:E30-9. 2005
    ..Overall, these findings demonstrate the important role of HSL on skeletal muscle, heart, and liver glucose metabolism...
  87. ncbi Mitochondrial dysfunction and type 2 diabetes
    Bradford B Lowell
    Department of Medicine, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Harvard Medical School, Boston, MA 02215, USA
    Science 307:384-7. 2005
    ..Emerging evidence supports the potentially unifying hypothesis that both of these prominent features of type 2 diabetes are caused by mitochondrial dysfunction...
  88. ncbi Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice
    Jiandie Lin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 119:121-35. 2004
    ..These data illustrate a central role for PGC-1alpha in the control of energy metabolism but also reveal novel systemic compensatory mechanisms and pathogenic effects of impaired energy homeostasis...
  89. ncbi PKC-theta knockout mice are protected from fat-induced insulin resistance
    Jason K Kim
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8020, USA
    J Clin Invest 114:823-7. 2004
    ..In conclusion, our findings demonstrate that PKC-theta is a crucial component mediating fat-induced insulin resistance in skeletal muscle and suggest that PKC-theta is a potential therapeutic target for the treatment of type 2 diabetes...
  90. ncbi 13C NMR isotopomer analysis of anaplerotic pathways in INS-1 cells
    Gary W Cline
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    J Biol Chem 279:44370-5. 2004
    ....
  91. ncbi Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease
    Varman T Samuel
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 279:32345-53. 2004
    ....
  92. ncbi Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation
    Qian Gao
    Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 101:4661-6. 2004
    ..Thus, STAT3 in the CNS plays essential roles in the regulation of energy homeostasis and reproduction...
  93. ncbi Transgenic overexpression of protein-tyrosine phosphatase 1B in muscle causes insulin resistance, but overexpression with leukocyte antigen-related phosphatase does not additively impair insulin action
    Janice M Zabolotny
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 279:24844-51. 2004
    ..Lack of additive impairment of insulin signaling by PTP1B and LAR suggests that these PTPs have overlapping actions in causing insulin resistance in vivo...
  94. ncbi Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes
    Kitt Falk Petersen
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
    N Engl J Med 350:664-71. 2004
    ....
  95. ncbi Hepatic glycogen metabolism in type 1 diabetes after long-term near normoglycemia
    Martin G Bischof
    Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna Medical School, Vienna, Austria
    Diabetes 51:49-54. 2002
    ..05. In conclusion, combined long- and short-term intensified insulin substitution normalizes rates of hepatic glycogen synthesis but not the contribution of gluconeogenesis to glycogen synthesis in type 1 diabetes...

Research Grants36

  1. IN VIVO NMR STUDIES OF CARBOHYDRATE METABOLISM
    Gerald Shulman; Fiscal Year: 2002
    ..Such results have important implications for understanding the mechanism of insulin resistance in patients with type 2 diabetes and may help identify potential targets for therapy. ..
  2. Mechanisms of Fatty Acid Induced Insulin Resistance
    Gerald Shulman; Fiscal Year: 2003
    ..abstract_text> ..
  3. CELLULAR MECHANISMS OF INSULIN RESISTANCE IN HUMANS
    Gerald Shulman; Fiscal Year: 2004
    ..This information will enable the rational development of novel therapeutic agents to prevent or reverse this pathologic condition. ..
  4. Yale Mouse Metabolic Phenotyping Center
    Gerald Shulman; Fiscal Year: 2005
    ..abstract_text> ..
  5. Mechanisms of Fatty Acid Induced Insulin Resistance
    Gerald Shulman; Fiscal Year: 2006
    ..abstract_text> ..
  6. Mechanisms of Fat Induced Insulin Resistance
    Gerald Shulman; Fiscal Year: 2007
    ....
  7. Mechanisms of Fat Induced Insulin Resistance
    Gerald I Shulman; Fiscal Year: 2010
    ....
  8. NMR STUDIES OF GLYCOGEN METABOLISM IN HUMANS
    Gerald Shulman; Fiscal Year: 1999
    ....
  9. IN VIVO NMR STUDIES OF CARBOHYDRATE METABOLISM
    Gerald Shulman; Fiscal Year: 1993
    ..Besides giving insight to the pathogenesis of the diabetic state new techniques will be developed to study glucose metabolism in vivo which have the potential to do so in man...
  10. CELLULAR MECHANISMS OF INSULIN RESISTANCE IN HUMANS
    Gerald I Shulman; Fiscal Year: 2010
    ..It is anticipated that the results of these studies will yield important new insights into the causes of insulin resistance, which will lead to new therapies for T2DM. ..