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Gerald I Shulman

MD, PhD, MACP, MACE, FRCP
George R. Cowgill Professor of Medicine (Endocrinology) and Professor of Cellular And Molecular Physiology; Co-Director, Yale Diabetes Research Center, Internal Medicine

Research Summary

Insulin resistance is a major factor responsible for the pathogenesis of type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease (NAFLD)/ nonalcoholic steatohepatitis (NASH), obesity associated cancers and neurodegenerative disease. Over the last three decades my laboratory has pioneered the development and application of nuclear magnetic resonance spectroscopy combined with stable isotopes and GC-MS, LC-MS/MS analyses to assess tissue specific flux rates of glucose and fat metabolism in vivo in both humans and awake transgenic rodent models of insulin resistance in order to elucidate the molecular basis of insulin resistance. These studies have in turn provided paradigm-shifting insights into the cellular and molecular mechanisms of lipid-induced insulin resistance in liver and skeletal muscle which my group has established in both humans and rodent models of NAFLD and type 2 diabetes. Based on these studies, my group has now developed novel liver-targeted mitochondrial protonophores that reverse hyperlipidemia, insulin resistance, diabetes, NAFLD, NASH and liver fibrosis in rodent models of type 2 diabetes and NASH, which are now in clinical development. During my tenure at Yale, I have had the pleasure of mentoring well over 100 trainees, and more than three dozen of these trainees have gone on to direct their own research laboratories around the world.

Extensive Research Description

Non-Alcoholic SteatoHepatitis (NASH); liver targeted mitchondrial uncoupling for treatment of NAFLD/NASH

Coauthors

Research Interests

Endocrine System Diseases; Insulin Resistance; Molecular Biology; Physiology; Non-alcoholic Fatty Liver Disease; Chemicals and Drugs; Analytical, Diagnostic and Therapeutic Techniques and Equipment

Public Health Interests

Cardiovascular Diseases; Metabolism; Nutrition; Obesity

Selected Publications

  • Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosisZ J, M Z, L V, Y J, MA A, T S, FY D, AM R, I C, JW K, M W, EA A, CL M, JP C, GI S, L T, ED R, CD G, BM S, KJ S. Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis 2022 DOI: 10.1530/ey.19.11.3.
  • Abstract P3032: Liver-directed Mitochondrial Uncoupling Attenuates The Progression Of Early And Late-stage Atherosclerosis In MiceGoedeke L, Zhang X, Sun J, Canfran-Duque A, Rotllan N, Nasiri A, Kahn M, Zhang X, Hernando C, Shulman G. Abstract P3032: Liver-directed Mitochondrial Uncoupling Attenuates The Progression Of Early And Late-stage Atherosclerosis In Mice Circulation Research 2022, 131: ap3032-ap3032. DOI: 10.1161/res.131.suppl_1.p3032.
  • SAT052 The PNPLA3 I148M variant increases intrahepatic lipolysis and beta oxidation and decreases de novo lipogenesis and hepatic mitochondrial function in humansLuukkonen P, Porthan K, Ahlholm N, Rosqvist F, Dufour S, Zhang X, Dabek J, Lehtimäki T, Seppänen W, Orho-Melander M, Hodson L, Petersen K, Shulman G, Yki-Järvinen H. SAT052 The PNPLA3 I148M variant increases intrahepatic lipolysis and beta oxidation and decreases de novo lipogenesis and hepatic mitochondrial function in humans Journal Of Hepatology 2022, 77: s690-s691. DOI: 10.1016/s0168-8278(22)01698-1.
  • SAT104 The effect of glucagon on rates of hepatic mitochondrial oxidation and pyruvate carboxylase flux in man assessed by positional isotopomer tracer analysis (PINTA)Petersen K, Shulman G. SAT104 The effect of glucagon on rates of hepatic mitochondrial oxidation and pyruvate carboxylase flux in man assessed by positional isotopomer tracer analysis (PINTA) Journal Of Hepatology 2022, 77: s714-s715. DOI: 10.1016/s0168-8278(22)01746-9.
  • 122-LB: Effect of Dapagliflozin on Mitochondrial Metabolism and Cardiac Function in the Failing HeartGOEDEKE L, MA Y, ZHANG J, GUERRERA N, WU X, ZHANG D, KAHN M, ZHANG X, YOUNG L, SHULMAN G. 122-LB: Effect of Dapagliflozin on Mitochondrial Metabolism and Cardiac Function in the Failing Heart Diabetes 2022, 71 DOI: 10.2337/db22-122-lb.
  • 219-LB: The Mitochondrial Calcium Uniporter Regulates Hepatic Lipid Accumulation and Mitochondrial OxidationLAMOIA T, HUBBARD B, GUERRA M, GOODMAN R, NATHANSON M, MOOTHA V, SHULMAN G. 219-LB: The Mitochondrial Calcium Uniporter Regulates Hepatic Lipid Accumulation and Mitochondrial Oxidation Diabetes 2022, 71 DOI: 10.2337/db22-219-lb.
  • 1336-P: FoxO1-ATGL-Sirt1-FoxO1 Feed Forward Signaling Mediates Effects on Hepatic Gene Expression and Glucose Homeostasis in LIRKO MiceO-SULLIVAN I, BHATTACHARYYA S, LIEW C, LEE S, CORDOBA-CHACON J, PERRY R, SHULMAN G, UNTERMAN T. 1336-P: FoxO1-ATGL-Sirt1-FoxO1 Feed Forward Signaling Mediates Effects on Hepatic Gene Expression and Glucose Homeostasis in LIRKO Mice Diabetes 2022, 71 DOI: 10.2337/db22-1336-p.
  • 195-OR: A Novel 13C5 Glutamine Tracer Method (Q Flux) Reveals a Key Role of Succinyl CoA Anaplerosis in Promoting Increased Rates of Hepatic Gluconeogenesis during HyperglucagonemiaHUBBARD B, SHULMAN G. 195-OR: A Novel 13C5 Glutamine Tracer Method (Q Flux) Reveals a Key Role of Succinyl CoA Anaplerosis in Promoting Increased Rates of Hepatic Gluconeogenesis during Hyperglucagonemia Diabetes 2022, 71 DOI: 10.2337/db22-195-or.
  • Human Kallistatin Ameliorates Insulin Resistance in Diet Induced Obese MiceSandforth L, Reinke J, Brachs S, Willmes D, McBride J, Peter A, Spranger J, Ma J, Shulman G, Jordan J, Haufe S, Birkenfeld A. Human Kallistatin Ameliorates Insulin Resistance in Diet Induced Obese Mice Diabetologie Und Stoffwechsel 2022, 17: s14-s15. DOI: 10.1055/s-0042-1746251.
  • 323-OR: SGLT2 Inhibition Promotes Myocardial Ketone Utilization in the Normal and Failing HeartGOEDEKE L, GOEDEKE L, LEE J, LEE J, MA Y, MA Y, HU X, ZHANG J, ZHANG J, DONG J, GALSGAARD K, GALSGAARD K, GUERRERA N, GUERRERA N, HAEDERSDAL S, HAEDERSDAL S, ZHANG X, PERRY R, CLINE G, YOUNG L, SHULMAN G. 323-OR: SGLT2 Inhibition Promotes Myocardial Ketone Utilization in the Normal and Failing Heart Diabetes 2021, 70 DOI: 10.2337/db21-323-or.
  • 281-OR: Endothelial Cell Cd36 Regulates Systemic Glucose and Lipid MetabolismGOEDEKE L, SON N, LAMOIA T, NASIRI A, KAHN M, ZHANG X, CLINE G, GOLDBERG I, SHULMAN G. 281-OR: Endothelial Cell Cd36 Regulates Systemic Glucose and Lipid Metabolism Diabetes 2021, 70 DOI: 10.2337/db21-281-or.
  • 335-OR: Lipid-Induced Insulin Resistance in the Renal Cortex Is Associated with Plasma Membrane Sn-1,2-diacylglycerol Accumulation and PKCe TranslocationHUBBARD B, GASPAR R, ZHANG D, KAHN M, NASIRI A, ZHANG X, CLINE G, SHULMAN G. 335-OR: Lipid-Induced Insulin Resistance in the Renal Cortex Is Associated with Plasma Membrane Sn-1,2-diacylglycerol Accumulation and PKCe Translocation Diabetes 2021, 70 DOI: 10.2337/db21-335-or.
  • 501-P: Lower Plasma Membrane Sn-1,2-Diacylglycerol Content and PKCepsilon/theta Activity Explain the Athlete’s ParadoxGASPAR R, LYU K, HUBBARD B, LEITNER B, LUUKKONEN P, HIRABARA S, SAKUMA I, NASIRI A, ZHANG D, KAHN M, CLINE G, PAULI J, PERRY R, PETERSEN K, SHULMAN G. 501-P: Lower Plasma Membrane Sn-1,2-Diacylglycerol Content and PKCepsilon/theta Activity Explain the Athlete’s Paradox Diabetes 2021, 70 DOI: 10.2337/db21-501-p.
  • 282-OR: The Effect of Glucagon on Rates of Hepatic Mitochondrial Oxidation and Pyruvate Carboxylase Flux in Man Assessed by Positional Isotopomer NMR Tracer Analysis (PINTA)PETERSEN K, SHULMAN G. 282-OR: The Effect of Glucagon on Rates of Hepatic Mitochondrial Oxidation and Pyruvate Carboxylase Flux in Man Assessed by Positional Isotopomer NMR Tracer Analysis (PINTA) Diabetes 2021, 70 DOI: 10.2337/db21-282-or.
  • A Single Virtual Consult Reduces Severe Hyperglycemia in Patients Admitted with COVID19 InfectionAthonvarangkul D, Gunawan F, Gunawan F, Nagel K, Nagel K, Bak L, Bak L, Herold K, Hwang J, Jastreboff A, Kibbey R, Shulman G, Vatner D, Alausa J, Alausa J, Subair L, Subair L, Inzucchi S. A Single Virtual Consult Reduces Severe Hyperglycemia in Patients Admitted with COVID19 Infection Journal Of The Endocrine Society 2021, 5: a335-a335. PMCID: PMC8089507, DOI: 10.1210/jendso/bvab048.683.
  • Leptin’s hunger-suppressing effects are mediated by the hypothalamic–pituitary–adrenocortical axis in rodentsRJ P, JM R, AM D, JC M, A R, H K, C W, JD S, BB L, GI S. Leptin’s hunger-suppressing effects are mediated by the hypothalamic–pituitary–adrenocortical axis in rodents 2020 DOI: 10.1530/ey.17.11.6.
  • Leptin mediates postprandial increases in body temperature through hypothalamus–adrenal medulla–adipose tissue crosstalkRJ P, K L, A R, J D, X L, Y Y, H Q, A W, X Y, GI S. Leptin mediates postprandial increases in body temperature through hypothalamus–adrenal medulla–adipose tissue crosstalk 2020 DOI: 10.1530/ey.17.11.7.
  • AS018 Carbohydrate restriction reverses NAFLD by altering hepatic mitochondrial fluxes in humansLuukkonen P, Dufour S, Lyu K, Zhang X, Hakkarainen A, Lehtimäki T, Cline G, Petersen K, Shulman G, Yki-Järvinen H. AS018 Carbohydrate restriction reverses NAFLD by altering hepatic mitochondrial fluxes in humans Journal Of Hepatology 2020, 73: s14. DOI: 10.1016/s0168-8278(20)30588-2.
  • 205-OR: Hepatic Protein Kinase C-e Is Necessary and Sufficient in Mediating Lipid-Induced Hepatic Insulin ResistanceLYU K, ZHANG D, KAHN M, RODRIGUES M, HIRABARA S, LUUKKONEN P, LEE S, BHANOT S, RINEHART J, BLUME N, RASCH M, SERLIE M, BOGAN J, CLINE G, SAMUEL V, SHULMAN G. 205-OR: Hepatic Protein Kinase C-e Is Necessary and Sufficient in Mediating Lipid-Induced Hepatic Insulin Resistance Diabetes 2020, 69 DOI: 10.2337/db20-205-or.
  • 1713-P: Adipocyte O-GlcNAc Transferase Regulate Adipogenesis through De Novo Lipogenesis in MiceMORINO K, TSUJI A, OHASHI N, IDA S, PERRY R, UGI S, FUJITA Y, SHULMAN G, MAEGAWA H. 1713-P: Adipocyte O-GlcNAc Transferase Regulate Adipogenesis through De Novo Lipogenesis in Mice Diabetes 2020, 69 DOI: 10.2337/db20-1713-p.
  • 459-P: Liver-Targeted Mitochondrial Uncoupling by CRMP Improves Whole-Body Insulin Sensitivity and Attenuates Atherosclerosis in A LDLR-/- Mouse Model of Metabolic SyndromeGOEDEKE L, ROTLLAN N, TOUSSAINT K, NASIRI A, ZHANG X, LEE J, ZHANG X, FERNÁNDEZ-HERNANDO C, SHULMAN G. 459-P: Liver-Targeted Mitochondrial Uncoupling by CRMP Improves Whole-Body Insulin Sensitivity and Attenuates Atherosclerosis in A LDLR-/- Mouse Model of Metabolic Syndrome Diabetes 2020, 69 DOI: 10.2337/db20-459-p.
  • 220-LB: Glucagon Promotes Hepatic Autophagy by AMPK-Mediated mTORC1 InhibitionGALSGAARD K, WEWER ALBRECHTSEN N, HOLST J, SHULMAN G, PETERSEN K, NASIRI A, CLINE G, ZHANG X, LEE J, HUBBARD B. 220-LB: Glucagon Promotes Hepatic Autophagy by AMPK-Mediated mTORC1 Inhibition Diabetes 2020, 69 DOI: 10.2337/db20-220-lb.
  • 224-LB: Role of the Mitochondrial Calcium Uniporter in the Regulation of Hepatic Mitochondrial Metabolism and GluconeogenesisLAMOIA T, LEE J, GUERRA M, GOODMAN R, SHULMAN G. 224-LB: Role of the Mitochondrial Calcium Uniporter in the Regulation of Hepatic Mitochondrial Metabolism and Gluconeogenesis Diabetes 2020, 69 DOI: 10.2337/db20-224-lb.
  • MON-635 FDXR Regulates Iron Metabolism and Glucose Metabolism in LiverSakuma I, Yokoyama M, Yamagata K, Hashimoto N, Nakayama A, Shulman G, Tanaka T. MON-635 FDXR Regulates Iron Metabolism and Glucose Metabolism in Liver Journal Of The Endocrine Society 2020, 4: mon-635. PMCID: PMC7207756, DOI: 10.1210/jendso/bvaa046.1557.
  • Non‐alcoholic Fatty Liver Disease and Insulin ResistancePetersen M, Samuel V, Petersen K, Shulman G. Non‐alcoholic Fatty Liver Disease and Insulin Resistance 2020, 455-471. DOI: 10.1002/9781119436812.ch37.
  • Abstract 797: Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidationRabin-Court A, Shulman G, Perry R. Abstract 797: Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidation Cancer Research 2019, 79: 797-797. DOI: 10.1158/1538-7445.am2019-797.
  • Abstract 797: Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidationRabin-Court A, Shulman G, Perry R. Abstract 797: Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidation 2019, 797-797. DOI: 10.1158/1538-7445.sabcs18-797.
  • 99-OR: Leptin Mediates Postprandial Thermogenesis through a Hypothalamic-Adrenomedullary-BAT AxisPERRY R, RABIN-COURT A, DONG J, LYU K, LI X, SHULMAN G. 99-OR: Leptin Mediates Postprandial Thermogenesis through a Hypothalamic-Adrenomedullary-BAT Axis Diabetes 2019, 68 DOI: 10.2337/db19-99-or.
  • 266-OR: Plasma Membrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin ResistanceLYU K, ZHANG Y, ZHANG D, KAHN M, NOZAKI Y, BHANOT S, BOGAN J, CLINE G, SAMUEL V, SHULMAN G. 266-OR: Plasma Membrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin Resistance Diabetes 2019, 68 DOI: 10.2337/db19-266-or.
  • 19-OR: Controlled-Release Mitochondrial Protonophore (CRMP) Reverses Hypertriglyceridemia and Hepatic Steatosis in Dysmetabolic Nonhuman PrimatesGOEDEKE L, ROMERAL V, BUTRICO G, KAHN M, DUFOUR S, ZHANG X, CLINE G, PETERSEN K, CHNG K, SHULMAN G. 19-OR: Controlled-Release Mitochondrial Protonophore (CRMP) Reverses Hypertriglyceridemia and Hepatic Steatosis in Dysmetabolic Nonhuman Primates Diabetes 2019, 68 DOI: 10.2337/db19-19-or.
  • 165-OR: The Mechanisms by Which Adiponectin Reverses Insulin Resistance in High-Fat Diet Fed MiceLI X, ZHANG D, PERRY R, VATNER D, GOEDEKE L, ZHANG Y, SHULMAN G. 165-OR: The Mechanisms by Which Adiponectin Reverses Insulin Resistance in High-Fat Diet Fed Mice Diabetes 2019, 68 DOI: 10.2337/db19-165-or.
  • 288-LB: Effects of the Hepatic Mitochondrial Calcium Uniporter on Hepatic Gluconeogenesis and Mitochondrial Metabolism in Awake MiceLEE J, GOEDEKE L, ZHANG Y, PERRY R, GOODMAN R, MOOTHA V, SHULMAN G. 288-LB: Effects of the Hepatic Mitochondrial Calcium Uniporter on Hepatic Gluconeogenesis and Mitochondrial Metabolism in Awake Mice Diabetes 2019, 68 DOI: 10.2337/db19-288-lb.
  • 97-OR: Leptin's Hunger-Suppressing Effects Are Mediated by the Hypothalamic-Pituitary-Adrenocortical AxisPERRY R, RESCH J, DOUGLASS A, MADARA J, SONG J, WU C, LOWELL B, SHULMAN G. 97-OR: Leptin's Hunger-Suppressing Effects Are Mediated by the Hypothalamic-Pituitary-Adrenocortical Axis Diabetes 2019, 68 DOI: 10.2337/db19-97-or.
  • 1782-P: Mechanism of Lipid-Induced White Adipose Tissue Insulin ResistanceZHANG Y, ZHANG D, LYU K, SONG J, LI X, PERRY R, SAMUEL V, SHULMAN G. 1782-P: Mechanism of Lipid-Induced White Adipose Tissue Insulin Resistance Diabetes 2019, 68 DOI: 10.2337/db19-1782-p.
  • 283-LB: Dissociating Insulin Signaling and SREBP1c Action from the Lipogenic Drive Seen in Human and Murine Hepatic Insulin ResistanceVATNER D, TER HORST K, GOEDEKE L, ZHANG D, SAMUEL V, SERLIE M, SHULMAN G. 283-LB: Dissociating Insulin Signaling and SREBP1c Action from the Lipogenic Drive Seen in Human and Murine Hepatic Insulin Resistance Diabetes 2019, 68 DOI: 10.2337/db19-283-lb.
  • 225-OR: Key Role for Glucose-Alanine Cycling in the Regulation of Hepatic Mitochondrial Oxidation during Starvation in HumansPETERSEN K, DUFOUR S, CLINE G, SHULMAN G. 225-OR: Key Role for Glucose-Alanine Cycling in the Regulation of Hepatic Mitochondrial Oxidation during Starvation in Humans Diabetes 2019, 68 DOI: 10.2337/db19-225-or.
  • Mechanisms by Which Glucagon Acutely Stimulates Hepatic Mitochondrial Oxidation and GluconeogenesisPERRY R, WANG Y, BRILL A, PENG L, ZHANG D, DUFOUR S, ZHANG Y, ZHANG X, NOZAKI Y, CLINE G, EHRLICH B, PETERSEN K, SHULMAN G. Mechanisms by Which Glucagon Acutely Stimulates Hepatic Mitochondrial Oxidation and Gluconeogenesis Diabetes 2018, 67 DOI: 10.2337/db18-146-or.
  • Metabolic Inflexibility Revisited—Muscle Substrate Oxidation Is Mechanistically Dissociated from Muscle Insulin Resistance in RatsSONG J, PERRY R, MUNK A, ZHANG Y, ZHANG D, SHULMAN G. Metabolic Inflexibility Revisited—Muscle Substrate Oxidation Is Mechanistically Dissociated from Muscle Insulin Resistance in Rats Diabetes 2018, 67 DOI: 10.2337/db18-240-lb.
  • Mechanism by Which Dapagliflozin Induces Euglycemic Ketoacidosis in RatsPERRY R, SONG J, WANG Y, SHULMAN G. Mechanism by Which Dapagliflozin Induces Euglycemic Ketoacidosis in Rats Diabetes 2018, 67 DOI: 10.2337/db18-254-or.
  • Evidence against Pathway-Selective Hepatic Insulin Resistance in MiceVATNER D, PETERSEN M, LI X, ROGERS J, CLINE G, SAMUEL V, SHULMAN G. Evidence against Pathway-Selective Hepatic Insulin Resistance in Mice Diabetes 2018, 67 DOI: 10.2337/db18-1766-p.
  • Membrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin Resistance In VivoLYU K, ZHANG D, NOZAKI Y, ZHANG Y, BHANOT S, CLINE G, SAMUEL V, SHULMAN G. Membrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin Resistance In Vivo Diabetes 2018, 67 DOI: 10.2337/db18-243-lb.
  • Effect of a Controlled-Release Mitochondrial Protonophore (CRMP) on Healthspan and Lifespan in MiceGOEDEKE L, CAMPOREZ J, NASIRI A, WANG Y, ZHANG X, SHULMAN G. Effect of a Controlled-Release Mitochondrial Protonophore (CRMP) on Healthspan and Lifespan in Mice Diabetes 2018, 67 DOI: 10.2337/db18-123-lb.
  • Unraveling the Athlete’s Paradox—Higher Insulin Sensitivity and Lower PKC? Activation Despite Higher Bioactive Lipids in Endurance-Trained AthletesPESTA D, ANADOL-SCHMITZ E, GANCHEVA S, MARKGRAF D, ZAHARIA O, KATSUYAMA H, KUPRIYANOVA Y, HWANG J, ZHANG D, SHULMAN G, RODEN M. Unraveling the Athlete’s Paradox—Higher Insulin Sensitivity and Lower PKC? Activation Despite Higher Bioactive Lipids in Endurance-Trained Athletes Diabetes 2018, 67 DOI: 10.2337/db18-267-lb.
  • THU-450 Mechanism for hypertriglyceridemia and effect of fibrate coadministration during acetyl-CoA carboxylase inhibitor treatmentGoedeke L, Bates J, Vatner D, Perry R, Ellis M, Wang T, Subramanian M, Myers R, Ray A, Shulman G. THU-450 Mechanism for hypertriglyceridemia and effect of fibrate coadministration during acetyl-CoA carboxylase inhibitor treatment Journal Of Hepatology 2018, 68: s333. DOI: 10.1016/s0168-8278(18)30885-7.
  • Fatty liver and whole-body insulin resistance relate to myocardial lipotoxicityHernandez E, Jelenik T, Fl?gel U, Rothe M, Rokitta I, Shulman G, Roden M, Szendroedi J. Fatty liver and whole-body insulin resistance relate to myocardial lipotoxicity Diabetologie Und Stoffwechsel 2017, 12: s1-s84. DOI: 10.1055/s-0037-1601610.
  • Insulin Resistance in Type 2 DiabetesRoden M, Petersen K, Shulman G. Insulin Resistance in Type 2 Diabetes 2016, 174-186. DOI: 10.1002/9781118924853.ch13.
  • Chapter 43 Metabolic SyndromeRuderman N, Shulman G. Chapter 43 Metabolic Syndrome 2016, 752-769.e7. DOI: 10.1016/b978-0-323-18907-1.00043-3.
  • Abstract 15983: Increased Mitochondrial Reactive Oxygen Species Lead to Deleterious JNK Signaling and Ischemia-Reperfusion Injury in AMPK-Inactivated HeartsZaha V, Qi D, Lee H, Hu X, Wu X, Shulman G, Rabinovitch P, Young L. Abstract 15983: Increased Mitochondrial Reactive Oxygen Species Lead to Deleterious JNK Signaling and Ischemia-Reperfusion Injury in AMPK-Inactivated Hearts Circulation 2014, 130 DOI: 10.1161/circ.130.suppl_2.15983.
  • I'm not Dead Yet: Flies and MiceBirkenfeld A, Samuel V, Shulman G, De Cabo R, Reenan R, Zhu C, Helfand S. I'm not Dead Yet: Flies and Mice Biophysical Journal 2014, 106: 12a. DOI: 10.1016/j.bpj.2013.11.118.
  • In Vivo NMR Studies on the Mechanism of Lipid-Induced Insulin Resistance in HumansShulman G. In Vivo NMR Studies on the Mechanism of Lipid-Induced Insulin Resistance in Humans Biophysical Journal 2014, 106: 12a. DOI: 10.1016/j.bpj.2013.11.119.
  • Muskuläre PKCΘ Aktivierung durch Diacylglyzerole führt zur Hemmung des proximalen Insulinsignalweges und reduzierter Glukoseaufnahme im Skelettmuskel von MenschenSzendrödi J, Yoshimura T, Phielix E, Koliaki C, Marcucci M, Zhang D, Jelenik T, Herder C, Nowotny P, Shulman G, Roden M. Muskuläre PKCΘ Aktivierung durch Diacylglyzerole führt zur Hemmung des proximalen Insulinsignalweges und reduzierter Glukoseaufnahme im Skelettmuskel von Menschen Diabetologie Und Stoffwechsel 2013, 8 DOI: 10.1055/s-0033-1341861.
  • Abstract 140: LRP6 Influences Body Fat and Glucose Homeostasis in Mouse by Activating mTOR Pathway and Inhibiting Mitochondrial Energy ExpenditureLiu W, Singh R, Choi C, Young L, Keramati A, Samuel V, Lifton R, Shulman G, Mani A. Abstract 140: LRP6 Influences Body Fat and Glucose Homeostasis in Mouse by Activating mTOR Pathway and Inhibiting Mitochondrial Energy Expenditure Arteriosclerosis Thrombosis And Vascular Biology 2012, 32 DOI: 10.1161/atvb.32.suppl_1.a140.
  • Deletion of the Mammalian INDY Homolog Mimics Aspects of Dietary Restriction and Protects against Adiposity and Insulin Resistance in MiceBirkenfeld A, Lee H, Guebre-Egziabher F, Alves T, Jurczak M, Jornayvaz F, Zhang D, Hsiao J, Martin-Montalvo A, Fischer-Rosinsky A, Spranger J, Pfeiffer A, Jordan J, Fromm M, König J, Lieske S, Carmean C, Frederick D, Weismann D, Knauf F, Irusta P, De Cabo R, Helfand S, Samuel V, Shulman G. Deletion of the Mammalian INDY Homolog Mimics Aspects of Dietary Restriction and Protects against Adiposity and Insulin Resistance in Mice Cell Metabolism 2011, 14: 567. DOI: 10.1016/j.cmet.2011.09.005.
  • Reply to Monetti et al.: Hepatic steatosis and diacylglycerol-mediated hepatic insulin resistance in acyl-CoA:diacylglycerol acyltransferase 2 (DGAT2) transgenic miceJornayvaz F, Jurczak M, Samuel V, Shulman G. Reply to Monetti et al.: Hepatic steatosis and diacylglycerol-mediated hepatic insulin resistance in acyl-CoA:diacylglycerol acyltransferase 2 (DGAT2) transgenic mice Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: e524-e524. PMCID: PMC3161525, DOI: 10.1073/pnas.1109195108.
  • PPARγ-induced cardiolipotoxicity in mice is ameliorated by PPARα deficiency despite increases in fatty acid oxidationSon N, Yu S, Tuinei J, Arai K, Hamai H, Homma S, Shulman G, Abel E, Goldberg I. PPARγ-induced cardiolipotoxicity in mice is ameliorated by PPARα deficiency despite increases in fatty acid oxidation Journal Of Clinical Investigation 2010, 120: 4583-4583. PMCID: PMC5477559, DOI: 10.1172/jci40905e1.
  • Resistance to High-fat Diet-Induced Obesity and Insulin Resistance in Mice with Very Long-Chain Acyl-CoA Dehydrogenase DeficiencyZhang D, Christianson J, Liu Z, Tian L, Choi C, Neschen S, Dong J, Wood P, Shulman G. Resistance to High-fat Diet-Induced Obesity and Insulin Resistance in Mice with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency Cell Metabolism 2010, 12: 103. DOI: 10.1016/j.cmet.2010.06.004.
  • Chapter 44 The Metabolic SyndromeRuderman N, Shulman G. Chapter 44 The Metabolic Syndrome 2010, 822-839. DOI: 10.1016/b978-1-4160-5583-9.00044-7.
  • Insulin ResistanceSamuel V, Petersen K, Shulman G. Insulin Resistance 2009, 469-483. DOI: 10.1002/9780470747919.ch31.
  • Erratum: UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicalsAndrews Z, Liu Z, Walllingford N, Erion D, Borok E, Friedman J, Tschöp M, Shanabrough M, Cline G, Shulman G, Coppola A, Gao X, Horvath T, Diano S. Erratum: UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals Nature 2009, 459: 736-736. DOI: 10.1038/nature08132.
  • CHAPTER 58 METABOLISMShulman G, Petersen K. CHAPTER 58 METABOLISM 2009, 1213-1236. DOI: 10.1016/b978-1-4160-3115-4.50061-5.
  • Correction: A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and MiceSavage D, Zhai L, Ravikumar B, Choi C, Snaar J, McGuire A, Wou S, Medina-Gomez G, Kim S, Bock C, Segvich D, Solanky B, Deelchand D, Vidal-Puig A, Wareham N, Shulman G, Karpe F, Taylor R, Pederson B, Roach P, O'Rahilly S, DePaoli-Roach A. Correction: A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice PLOS Medicine 2008, 5: e246. PMCID: PMC2605894, DOI: 10.1371/journal.pmed.0050246.
  • Muscle-specific knockout of PKC-λ impairs glucose transport and induces metabolic and diabetic syndromesFarese R, Sajan M, Yang H, Li P, Mastorides S, Gower W, Nimal S, Choi C, Kim S, Shulman G, Kahn C, Braun U, Leitges M. Muscle-specific knockout of PKC-λ impairs glucose transport and induces metabolic and diabetic syndromes Journal Of Clinical Investigation 2007, 117: 3141-3141. PMCID: PMC1994612, DOI: 10.1172/jci31408c1.
  • IntroductionRitz E, Fujita T, Shulman G. Introduction The American Journal Of Medicine 2006, 119: s1-s2. DOI: 10.1016/j.amjmed.2006.01.007.
  • MRS Studies of the Role of the Muscle Glycogen Synthesis Pathway in the Pathophysiology of Type 2 DiabetesShulman G, Rothman D. MRS Studies of the Role of the Muscle Glycogen Synthesis Pathway in the Pathophysiology of Type 2 Diabetes 2005, 45-57. DOI: 10.1002/0470011505.ch4.
  • Insulin Resistance in NAFLD: Potential Mechanisms and TherapiesSamuel V, Shulman G. Insulin Resistance in NAFLD: Potential Mechanisms and Therapies 2004, 38-54. DOI: 10.1002/9780470987438.ch4.
  • 26 IMPAIRED MITOCHONDRIAL ACTIVITY IN INSULIN RESISTANT OFFSPRING OF TYPE 2 DIABETICS.Petersen K, Dufour S, Befroy D, Garcia R, Shulman G. 26 IMPAIRED MITOCHONDRIAL ACTIVITY IN INSULIN RESISTANT OFFSPRING OF TYPE 2 DIABETICS. Journal Of Investigative Medicine 2004, 52: s381. DOI: 10.1136/jim-52-suppl2-100.
  • IMPAIRED MITOCHONDRIAL ACTIVITY IN INSULIN RESISTANT OFFSPRING OF TYPE 2 DIABETICS.: 26Petersen K, Dufour S, Befroy D, Garcia R, Shulman G. IMPAIRED MITOCHONDRIAL ACTIVITY IN INSULIN RESISTANT OFFSPRING OF TYPE 2 DIABETICS.: 26 Journal Of Investigative Medicine 2004, 52: s381. DOI: 10.1097/00042871-200403002-00100.
  • Alterata attività mitocondriale nella prole insulino-resistente di pazienti con diabete di tipo 2Petersen K, Dufour S, Befroy D, Garcia R, Shulman G, Pezzino V. Alterata attività mitocondriale nella prole insulino-resistente di pazienti con diabete di tipo 2 L'Endocrinologo 2003, 4: 224-225. DOI: 10.1007/bf03344480.
  • Regulation of Hepatic Glucose UptakeTaylor R, Shulman G. Regulation of Hepatic Glucose Uptake 2001, 787-802. DOI: 10.1002/cphy.cp070226.
  • Activation of glucose transport in the ischemic heart: Translocation of GLUT4 and GLUT1 by 5′-AMP-activated protein kinaseYoung L, Russell R, Coven D, Shulman G, Sinusas A. Activation of glucose transport in the ischemic heart: Translocation of GLUT4 and GLUT1 by 5′-AMP-activated protein kinase Journal Of Molecular And Cellular Cardiology 2001, 33: a145. DOI: 10.1016/s0022-2828(01)90556-5.
  • 411. Measurement of the rate of pyruvate carboxylase in human brain by 13C MRSMason G, Petersen K, Shen J, Behar K, Petroff O, Shulman G, Rothman D. 411. Measurement of the rate of pyruvate carboxylase in human brain by 13C MRS Biological Psychiatry 2000, 47: s126. DOI: 10.1016/s0006-3223(00)00681-8.
  • 303. Measurement of human cortical GABA synthesis in vivoMason G, Petersen K, Shen J, Behar K, Petroff O, Shulman G, Rothman D. 303. Measurement of human cortical GABA synthesis in vivo Biological Psychiatry 2000, 47: s92. DOI: 10.1016/s0006-3223(00)00567-9.
  • Intramuscular Glycogen and Intramyocellular Lipid Utilization during Prolonged Exercise and Recovery in Man: A 13C and 1H Nuclear Magnetic Resonance Spectroscopy Study1Krssak M, Petersen K, Bergeron R, Price T, Laurent D, Rothman D, Roden M, Shulman G. Intramuscular Glycogen and Intramyocellular Lipid Utilization during Prolonged Exercise and Recovery in Man: A 13C and 1H Nuclear Magnetic Resonance Spectroscopy Study1 The Journal Of Clinical Endocrinology & Metabolism 2000, 85: 748-754. DOI: 10.1210/jcem.85.2.6354.
  • NMR Studies on the Mechanism of Insulin ResistancePerseghin G, Petersen K, Shulman G. NMR Studies on the Mechanism of Insulin Resistance 1999, 159-177. DOI: 10.1007/978-1-59259-716-1_9.
  • EFFECTIVENESS OF TWO CARBOHYDRATE LOADING PROTOCOLS TO ACHIEVE AND MAINTAIN SUPERCOMPENSATED MUSCLE GLYCOGENGoforth H, Schneider K, Prusaczyk W, Laurent D, Petersen K, Shulman G. EFFECTIVENESS OF TWO CARBOHYDRATE LOADING PROTOCOLS TO ACHIEVE AND MAINTAIN SUPERCOMPENSATED MUSCLE GLYCOGEN Medicine & Science In Sports & Exercise 1998, 30: 246. DOI: 10.1097/00005768-199805001-01401.
  • CAFFEINE HAS NO EFFECT ON MUSCLE GLYCOGEN USE DURING EXERCISE AFTER CARBOHYDRATE LOADINGPrusaczyk W, Schneider K, Laurent D, Goforth H, Petersen K, Shulman G. CAFFEINE HAS NO EFFECT ON MUSCLE GLYCOGEN USE DURING EXERCISE AFTER CARBOHYDRATE LOADING Medicine & Science In Sports & Exercise 1998, 30: 248. DOI: 10.1097/00005768-199805001-01410.
  • THE RELIABILITY OF THE HYPERINSULINEMIC/EUGLYCEMIC CLAMP IN ACTIVE HEALTHY ADULTS.L D, Petersen K, Shulman G, Nadel E. THE RELIABILITY OF THE HYPERINSULINEMIC/EUGLYCEMIC CLAMP IN ACTIVE HEALTHY ADULTS. Medicine & Science In Sports & Exercise 1998, 30: 245. DOI: 10.1097/00005768-199805001-01393.
  • Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional studyPerseghin G, Ghosh S, Gerow K, Shulman G. Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional study Diabetes 1997, 46: 1001-1009. DOI: 10.2337/diabetes.46.6.1001.
  • The effect of leptin is enhanced by microinjection into the ventromedial hypothalamusJacob R, Dziura J, Medwick M, Leone P, Caprio S, During M, Shulman G, Sherwin R. The effect of leptin is enhanced by microinjection into the ventromedial hypothalamus Diabetes 1997, 46: 150-152. DOI: 10.2337/diabetes.46.1.150.
  • Local ventromedial hypothalamus glucopenia triggers counterregulatory hormone releaseBorg W, Sherwin R, During M, Borg M, Shulman G. Local ventromedial hypothalamus glucopenia triggers counterregulatory hormone release Diabetes 1995, 44: 180-184. DOI: 10.2337/diabetes.44.2.180.
  • Contribution of hepatic glycogenolysis to glucose production in humans in response to a physiological increase in plasma glucagon concentrationMagnusson I, Rothman D, Gerard D, Katz L, Shulman G. Contribution of hepatic glycogenolysis to glucose production in humans in response to a physiological increase in plasma glucagon concentration Diabetes 1995, 44: 185-189. DOI: 10.2337/diabetes.44.2.185.
  • Inhibitory effect of pregnancy on counterregulatory hormone responses to hypoglycemia in awake ratRossi G, Lapaczewski P, Diamond M, Jacob R, Shulman G, Sherwin R. Inhibitory effect of pregnancy on counterregulatory hormone responses to hypoglycemia in awake rat Diabetes 1993, 42: 1440-1445. DOI: 10.2337/diabetes.42.10.1440.
  • Comparative effects of monomethylsuccinate and glucose on insulin secretion from perifused rat isletsZawalich W, Zawalich K, Cline G, Shulman G, Rasmussen H. Comparative effects of monomethylsuccinate and glucose on insulin secretion from perifused rat islets Diabetes 1993, 42: 843-850. DOI: 10.2337/diabetes.42.6.843.
  • Simultaneous insulinlike growth factor I and insulin resistance in obese Zucker ratsJacob R, Sherwin R, Greenawalt K, Shulman G. Simultaneous insulinlike growth factor I and insulin resistance in obese Zucker rats Diabetes 1992, 41: 691-697. DOI: 10.2337/diabetes.41.6.691.
  • Plasma level of 13,14-dihydro-15-keto-PGE2 in patients with diabetic ketoacidosis and in normal fasting subjectsAxelrod L, Shulman G, Blackshear P, Bornstein W, Roussell A, Aoki T. Plasma level of 13,14-dihydro-15-keto-PGE2 in patients with diabetic ketoacidosis and in normal fasting subjects Diabetes 1986, 35: 1004-1010. DOI: 10.2337/diabetes.35.9.1004.
  • A pulse sequence for simplifying hydrogen NMR spectra of biological tissuesRothman D, Arias-Mendoza F, Shulman G, Shulman R. A pulse sequence for simplifying hydrogen NMR spectra of biological tissues Journal Of Magnetic Resonance (1969) 1984, 60: 430-436. DOI: 10.1016/0022-2364(84)90054-4.

Clinical Trials

ConditionsStudy Title
Children's Health; Diseases of the Endocrine System; Immune SystemStudy to investigate adipocyte cell and lipid turnover in obese adolescents