Kitt Petersen, MD
Research & Publications
Biography
News
Research Summary
Clinical studies of the biochemical and molecular mechanisms of insulin action. My research interests include the study of normal physiologic regulation of metabolism during the fed and fasted state as well as during exercise as well as the metabolic disturbances, which occur with insulin resistance and diabetes. The studies include induction and reversal of insulin resistance in patients with Type 1 and 2 Diabetes, Prediabetic States, Obesity, Low Birth Weight and Aging. The studies involve the insulin clamp procedure in the 4T NMR instrument, in combination with stable istotope techniques and muscle biopsies to assess insulin action in liver, fat tissue and muscle.
In order to elucidate the physiologic regulations of insulin action as well as the defects in pathologic states, we use 13C and 31P NMR spectroscopic techniques using the 4T magnet to determine rate-limiting steps of insulin stimulated glucose metabolism in liver and muscle.* Lipid content of muscle and liver are assessed using 1H NMR spectroscopy also on the 4T instrument.* 13C NMR spectroscopy in combination with a 31P saturation transfer technique to assess rates of TCA cycle flux, ATP synthesis and energy coupling in muscle. * Natural abundance 13C NMR spectroscopy using the 4T instrument to measure liver glycogen concentrations in humans in combination with stable isotope techniques to determine rates of net hepatic glycogenolysis, and the relative contribution to whole body glucose production during short and long-term fasting, in patients with type 2 diabetes, Maturity Onset Diabetes of the Young (MODY), liver cirrhosis. * We are using 13C and 1H NMR spectroscopy at 4T to study the regulation of brain Metabolism (PC and TCA Flux and anaplerosis) in the elderly and in patients with type 1 diabetes, GDH defects and liver cirrhosis.
Coauthors
Research Interests
Endocrine System Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases
Public Health Interests
Aging; Bioinformatics; Biomarkers; Genetics, Genomics, Epigenetics; Metabolism; Nutrition; Obesity; Women's Health
Selected Publications
- 1569-P: Lysophosphatidic Acid Mediates Inflammation in Liver and White Adipose Tissue in a Rat Model of 1-acyl-sn-glycerol-3-phosphate Acyltransferase 2 DeficiencySAKUMA I, GASPAR R, LUUKKONEN P, KAHN M, MURRAY S, SAMUEL V, PETERSEN K, SHULMAN G. 1569-P: Lysophosphatidic Acid Mediates Inflammation in Liver and White Adipose Tissue in a Rat Model of 1-acyl-sn-glycerol-3-phosphate Acyltransferase 2 Deficiency Diabetes 2023, 72 DOI: 10.2337/db23-1569-p.
- Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitisLuukkonen P, Sakuma I, Gaspar R, Mooring M, Nasiri A, Kahn M, Zhang X, Zhang D, Sammalkorpi H, Penttilä A, Orho-Melander M, Arola J, Juuti A, Zhang X, Yimlamai D, Yki-Järvinen H, Petersen K, Shulman G. Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2217543120. PMID: 36669104, PMCID: PMC9942818, DOI: 10.1073/pnas.2217543120.
- Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained miceGaspar 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. Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice Diabetologia 2022, 66: 567-578. PMID: 36456864, DOI: 10.1007/s00125-022-05838-8.
- 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.
- 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.
- 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.
- 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.
- 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.
- Anti‐inflammatory effects of oestrogen mediate the sexual dimorphic response to lipid‐induced insulin resistanceCamporez JP, Lyu K, Goldberg EL, Zhang D, Cline GW, Jurczak MJ, Dixit VD, Petersen KF, Shulman GI. Anti‐inflammatory effects of oestrogen mediate the sexual dimorphic response to lipid‐induced insulin resistance The Journal Of Physiology 2019, 597: 3885-3903. PMID: 31206703, PMCID: PMC6876753, DOI: 10.1113/jp277270.
- 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.
- 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.
- 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.
- Diabetes in the ElderlyRosenquist K, Petersen K. Diabetes in the Elderly 2011, 493-496. DOI: 10.1007/978-1-4419-6999-6_39.
- Regulation of hepatic fat and glucose oxidation in rats with lipid‐induced hepatic insulin resistanceAlves TC, Befroy DE, Kibbey RG, Kahn M, Codella R, Carvalho RA, Petersen K, Shulman GI. Regulation of hepatic fat and glucose oxidation in rats with lipid‐induced hepatic insulin resistance Hepatology 2011, 53: 1175-1181. PMID: 21400553, PMCID: PMC3077048, DOI: 10.1002/hep.24170.
- Insulin ResistanceSamuel V, Petersen K, Shulman G. Insulin Resistance 2009, 469-483. DOI: 10.1002/9780470747919.ch31.
- Chapter 21 Assessment of In Vivo Mitochondrial Metabolism by Magnetic Resonance SpectroscopyBefroy DE, Petersen K, Rothman DL, Shulman GI. Chapter 21 Assessment of In Vivo Mitochondrial Metabolism by Magnetic Resonance Spectroscopy 2009, 457: 373-393. PMID: 19426879, PMCID: PMC3077057, DOI: 10.1016/s0076-6879(09)05021-6.
- CHAPTER 58 METABOLISMShulman G, Petersen K. CHAPTER 58 METABOLISM 2009, 1213-1236. DOI: 10.1016/b978-1-4160-3115-4.50061-5.
- The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndromePetersen KF, Dufour S, Savage DB, Bilz S, Solomon G, Yonemitsu S, Cline GW, Befroy D, Zemany L, Kahn BB, Papademetris X, Rothman DL, Shulman GI. The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 12587-12594. PMID: 17640906, PMCID: PMC1924794, DOI: 10.1073/pnas.0705408104.
- Type 2 Diabetes–Lessons Learned From Clinical StudiesPetersen K. Type 2 Diabetes–Lessons Learned From Clinical Studies The FASEB Journal 2006, 20: a1307-a1307. DOI: 10.1096/fasebj.20.5.a1307-c.
- 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.
- Impaired Mitochondrial Activity in Insulin resistant offspring of Type 2 DiabeticsPetersen K, Dufour S, Befroy D, Garcia R, Shulman G. Impaired Mitochondrial Activity in Insulin resistant offspring of Type 2 Diabetics Journal Of Investigative Medicine 2004, 52: 381-381. DOI: 10.1177/108155890405202s100.
- 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.
- Corrigendum to “A comparison of 13C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-13C]glucose” [Brain Research Protocols, 10 (2003) 181–190]☆Mason G, Petersen K, de Graaf R, Kanamatsu T, Otsuki T, Rothman D. Corrigendum to “A comparison of 13C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-13C]glucose” [Brain Research Protocols, 10 (2003) 181–190]☆ Brain Research 2003, 11: 143. DOI: 10.1016/s1385-299x(03)00021-7.
- Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscleLebon V, Dufour S, Petersen K, Ren J, Jucker B, Slezak L, Cline G, Rothman D, Shulman G. Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle Journal Of Clinical Investigation 2001, 108: 733-737. PMID: 11544279, PMCID: PMC209375, DOI: 10.1172/jci11775.
- Stimulating Effects of Low-Dose Fructose on Insulin-Stimulated Hepatic Glycogen Synthesis in HumansPetersen K, Laurent D, Yu C, Cline G, Shulman G. Stimulating Effects of Low-Dose Fructose on Insulin-Stimulated Hepatic Glycogen Synthesis in Humans Diabetes 2001, 50: 1263-1268. PMID: 11375325, DOI: 10.2337/diabetes.50.6.1263.
- Contribution of net hepatic glycogen synthesis to disposal of an oral glucose load in humansPetersen K, Cline G, Gerard D, Magnusson I, Rothman D, Shulman G. Contribution of net hepatic glycogen synthesis to disposal of an oral glucose load in humans Metabolism 2001, 50: 598-601. PMID: 11319724, DOI: 10.1053/meta.2001.22561.
- Effects of Caffeine on Muscle Glycogen Utilization and the Neuroendocrine Axis during ExerciseLaurent D, Schneider K, Prusaczyk W, Franklin C, Vogel S, Krssak M, Petersen K, Goforth H, Shulman G. Effects of Caffeine on Muscle Glycogen Utilization and the Neuroendocrine Axis during Exercise The Journal Of Clinical Endocrinology & Metabolism 2000, 85: 2170-2175. PMID: 10852448, DOI: 10.1210/jcem.85.6.6655.
- Mechanism of muscle glycogen autoregulation in humansLaurent D, Hundal R, Dresner A, Price T, Vogel S, Petersen K, Shulman G. Mechanism of muscle glycogen autoregulation in humans AJP Endocrinology And Metabolism 2000, 278: e663-e668. PMID: 10751200, DOI: 10.1152/ajpendo.2000.278.4.e663.
- 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.
- Glycogen loading alters muscle glycogen resynthesis after exercisePrice T, Laurent D, Petersen K, Rothman D, Shulman G. Glycogen loading alters muscle glycogen resynthesis after exercise Journal Of Applied Physiology 2000, 88: 698-704. PMID: 10658040, DOI: 10.1152/jappl.2000.88.2.698.
- 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.
- Impaired Glucose Transport as a Cause of Decreased Insulin-Stimulated Muscle Glycogen Synthesis in Type 2 DiabetesCline G, Petersen K, Krssak M, Shen J, Hundal R, Trajanoski Z, Inzucchi S, Dresner A, Rothman D, Shulman G. Impaired Glucose Transport as a Cause of Decreased Insulin-Stimulated Muscle Glycogen Synthesis in Type 2 Diabetes New England Journal Of Medicine 1999, 341: 240-246. PMID: 10413736, DOI: 10.1056/nejm199907223410404.
- Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMRShen J, Petersen K, Behar K, Brown P, Nixon T, Mason G, Petroff O, Shulman G, Shulman R, Rothman D. Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8235-8240. PMID: 10393978, PMCID: PMC22218, DOI: 10.1073/pnas.96.14.8235.
- Contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production in cirrhosisPetersen K, Krssak M, Navarro V, Chandramouli V, Hundal R, Schumann W, Landau B, Shulman G. Contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production in cirrhosis American Journal Of Physiology 1999, 276: e529-e535. PMID: 10070020, DOI: 10.1152/ajpendo.1999.276.3.e529.
- Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activityDresner A, Laurent D, Marcucci M, Griffin M, Dufour S, Cline G, Slezak L, Andersen D, Hundal R, Rothman D, Petersen K, Shulman G. Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity Journal Of Clinical Investigation 1999, 103: 253-259. PMID: 9916137, PMCID: PMC407880, DOI: 10.1172/jci5001.
- 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.
- Effect of epinephrine on muscle glycogenolysis and insulin-stimulated muscle glycogen synthesis in humansLaurent D, Petersen K, Russell R, Cline G, Shulman G. Effect of epinephrine on muscle glycogenolysis and insulin-stimulated muscle glycogen synthesis in humans American Journal Of Physiology 1998, 274: e130-e138. PMID: 9458758, DOI: 10.1152/ajpendo.1998.274.1.e130.
- Effects of insulin-like growth factor I on glucose metabolism in rats with liver cirrhosisPetersen K, Jacob R, West A, Sherwin R, Shulman G. Effects of insulin-like growth factor I on glucose metabolism in rats with liver cirrhosis American Journal Of Physiology 1997, 273: e1189-e1193. PMID: 9435535, DOI: 10.1152/ajpendo.1997.273.6.e1189.
- New insulins and other possible therapeutic approachesJohannesen J, Petersen K, Berger M, Binder C. New insulins and other possible therapeutic approaches Diabetologia 1997, 40: b89. PMID: 9345654, DOI: 10.1007/bf03168195.
- Triiodothyronine treatment increases substrate cycling between pyruvate carboxylase and malic enzyme in perfused rat liverPetersen K, Blair J, Shulman G. Triiodothyronine treatment increases substrate cycling between pyruvate carboxylase and malic enzyme in perfused rat liver Metabolism 1995, 44: 1380-1383. PMID: 7476321, DOI: 10.1016/0026-0495(95)90133-7.
- A liver factor increasing glucose uptake in rat hindquartersPetersen K, Tygstrup N. A liver factor increasing glucose uptake in rat hindquarters Journal Of Hepatology 1994, 20: 461-465. PMID: 8051382, DOI: 10.1016/s0168-8278(05)80490-8.
- Gluconeogenesis in hepatocytes determined with [2-13C] acetate and quantitative 13C NMR spectroscopyPetersen K, Grunnet N. Gluconeogenesis in hepatocytes determined with [2-13C] acetate and quantitative 13C NMR spectroscopy The International Journal Of Biochemistry & Cell Biology 1993, 25: 1-5. PMID: 8432377, DOI: 10.1016/0020-711x(93)90482-t.