Gerald I Shulman, MD, PhD, MACP, MACE, FRCP
Internal Medicine, Endocrinology
Titles
- George R. Cowgill Professor of Medicine (Endocrinology) and Professor of Cellular And Molecular Physiology
- Co-Director, Yale Diabetes Research Center, Internal Medicine
Education & Training
- Research FellowMassachusetts General Hospital/Harvard Medical School (1984)
- ResidentDuke University Medical Center (1981)
- MDWayne State University (1979)
- PhDWayne State University, Physiology (1979)
Additional Information
Honors & Recognitions
- Manpei Suzuki International Prize for Diabetes Research: Manpei Suzuki Diabetes Foundation (2021)
- Elected to Fellowship in the Royal College of Physicians: Royal College of Physicians (London) (2021)
- Elected to Mastership, American College of Physicians: American College of Physicians (2020)
- Samuel Eichold II Memorial Award for Contributions in Diabetes: American College of Physicians (2020)
- Arthur Riggs Award for Discoveries in the Basic Sciences: City of Hope (2019)
- Stanley Mirsky Award: Ichan School of Medicine (2019)
- Banting Medal for Scientific Achievement: American Diabetes Association (2018)
- Elected to the American Academy of Arts & Sciences: American Academy of Arts & Sciences (2018)
- Special Achievement Award: The Miami Winter Symposium (2017)
- Guyton Distinguished Visiting Professor Award: University of Mississippi (2017)
Board Certifications
- AB of Internal Medicine, Endocrinology & Metabolism (1985, recertified: 1985)
- AB of Internal Medicine, Internal Medicine (1982)
Professional Service
- Proceedings of the National Academy of Sciences (2021 - 2022): Member of the Editorial Board
- Science Translational Medicine (2013 - Present): Member of Editorial Board/Advisory Board
- Clinical and Translational Science (2008 - Present): Member of Editorial Board
- Cell Metabolism (2004 - Present): Member of Editorial Board
- Journal of Biological Chemistry (2002 - 2008): Member of Editorial Board
- American Journal of Physiology, Endocrinology/Metabolism (2001 - 2007): Member of Editorial Board
- Current Diabetes Reports (2001 - Present): Member of Editorial Board
- Journal of Clinical Investigation (1998 - Present): Member of Editorial Board
- International Journal of Molecular Medicine (1997 - 2005): Member of Editorial Board
- Diabetologia (1997 - 2001): Member of Editorial Board
Publications
- Huang Y, Zhou JH, Zhang H, Canfran-Duque A, Singh AK, Perry RJ, Shulman G, Fernandez-Hernando C, Min W. Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance. The Journal Of Clinical Investigation 2022, 132 PMID: 35202005, PMCID: PMC9057632, DOI: 10.1172/JCI148852.
- DeVito LM, Dennis EA, Kahn BB, Shulman GI, Witztum JL, Sadhu S, Nickels J, Spite M, Smyth S, Spiegel S. Bioactive lipids and metabolic syndrome-a symposium report. Annals Of The New York Academy Of Sciences 2022, 1511: 87-106. PMID: 35218041, PMCID: PMC9219555, DOI: 10.1111/nyas.14752.
- Petersen KF, Dufour S, Li F, Rothman DL, Shulman GI. Ethnic and sex differences in hepatic lipid content and related cardiometabolic parameters in lean individuals. JCI Insight 2022, 7 PMID: 35167495, PMCID: PMC9057590, DOI: 10.1172/jci.insight.157906.
- LaMoia TE, Butrico GM, Kalpage HA, Goedeke L, Hubbard BT, Vatner DF, Gaspar RC, Zhang XM, Cline GW, Nakahara K, Woo S, Shimada A, Hüttemann M, Shulman GI. Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2122287119. PMID: 35238637, PMCID: PMC8916010, DOI: 10.1073/pnas.2122287119.
- Bhat N, Narayanan A, Fathzadeh M, Kahn M, Zhang D, Goedeke L, Neogi A, Cardone RL, Kibbey RG, Fernandez-Hernando C, Ginsberg HN, Jain D, Shulman G, Mani A. Dyrk1b promotes hepatic lipogenesis by bypassing canonical insulin signaling and directly activating mTORC2 in mice. The Journal Of Clinical Investigation 2022, 132 PMID: 34855620, PMCID: PMC8803348, DOI: 10.1172/JCI153724.
- Goedeke L, Murt KN, Di Francesco A, Camporez JP, Nasiri AR, Wang Y, Zhang XM, Cline GW, de Cabo R, Shulman GI. Sex- and strain-specific effects of mitochondrial uncoupling on age-related metabolic diseases in high-fat diet-fed mice. Aging Cell 2022, 21: e13539. PMID: 35088525, PMCID: PMC8844126, DOI: 10.1111/acel.13539.
- Tarabra E, Nouws J, Vash-Margita A, Hellerstein M, Shabanova V, McCollum S, Pierpont B, Zhao D, Shulman GI, Caprio S. CIDEA expression in SAT from adolescent girls with obesity and unfavorable patterns of abdominal fat distribution. Obesity (Silver Spring, Md.) 2021, 29: 2068-2080. PMID: 34672413, PMCID: PMC8612981, DOI: 10.1002/oby.23295.
- Wang Q, Li D, Cao G, Shi Q, Zhu J, Zhang M, Cheng H, Wen Q, Xu H, Zhu L, Zhang H, Perry RJ, Spadaro O, Yang Y, He S, Chen Y, Wang B, Li G, Liu Z, Yang C, Wu X, Zhou L, Zhou Q, Ju Z, Lu H, Xin Y, Yang X, Wang C, Liu Y, Shulman GI, Dixit VD, Lu L, Yang H, Flavell RA, Yin Z. IL-27 signalling promotes adipocyte thermogenesis and energy expenditure. Nature 2021, 600: 314-318. PMID: 34819664, DOI: 10.1038/s41586-021-04127-5.
- Goedeke L, Canfrán-Duque A, Rotllan N, Chaube B, Thompson BM, Lee RG, Cline GW, McDonald JG, Shulman GI, Lasunción MA, Suárez Y, Fernández-Hernando C. MMAB promotes negative feedback control of cholesterol homeostasis. Nature Communications 2021, 12: 6448. PMID: 34750386, PMCID: PMC8575900, DOI: 10.1038/s41467-021-26787-7.
- Jiang Z, Zhao M, Voilquin L, Jung Y, Aikio MA, Sahai T, Dou FY, Roche AM, Carcamo-Orive I, Knowles JW, Wabitsch M, Appel EA, Maikawa CL, Camporez JP, Shulman GI, Tsai L, Rosen ED, Gardner CD, Spiegelman BM, Svensson KJ. Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis. Cell Metabolism 2021, 33: 1836-1852.e11. PMID: 34348115, PMCID: PMC8429235, DOI: 10.1016/j.cmet.2021.07.010.
- Schumann T, König J, von Loeffelholz C, Vatner DF, Zhang D, Perry RJ, Bernier M, Chami J, Henke C, Kurzbach A, El-Agroudy NN, Willmes DM, Pesta D, de Cabo R, O Sullivan JF, Simon E, Shulman GI, Hamilton BS, Birkenfeld AL. Publisher Correction: Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance. Communications Biology 2021, 4: 890. PMID: 34262128, PMCID: PMC8280181, DOI: 10.1038/s42003-021-02425-2.
- Schumann T, König J, von Loeffelholz C, Vatner DF, Zhang D, Perry RJ, Bernier M, Chami J, Henke C, Kurzbach A, El-Agroudy NN, Willmes DM, Pesta D, de Cabo R, O Sullivan JF, Simon E, Shulman GI, Hamilton BS, Birkenfeld AL. Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance. Communications Biology 2021, 4: 826. PMID: 34211098, PMCID: PMC8249653, DOI: 10.1038/s42003-021-02279-8.
- Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell 2021, 184: 2537-2564. PMID: 33989548, DOI: 10.1016/j.cell.2021.04.015.
- Petersen KF, Rothman D, Shulman GI. Reply to Carter et al.: An alternative hypothesis for why exposure to static magnetic and electric fields treats type 2 diabetes. American Journal Of Physiology. Endocrinology And Metabolism 2021, 320: E1003. PMID: 33843277, DOI: 10.1152/ajpendo.00120.2021.
- Petersen KF, Rothman D, Shulman GI. Point: An alternative hypothesis for why exposure to static magnetic and electric fields treats type 2 diabetes. American Journal Of Physiology. Endocrinology And Metabolism 2021, 320: E999-E1000. PMID: 33843279, DOI: 10.1152/ajpendo.00657.2020.
- Wijngaard R, Perramón M, Parra-Robert M, Hidalgo S, Butrico G, Morales-Ruiz M, Zeng M, Casals E, Jiménez W, Fernández-Varo G, Shulman GI, Cline GW, Casals G. Validation of a Gas Chromatography-Mass Spectrometry Method for the Measurement of the Redox State Metabolic Ratios Lactate/Pyruvate and β-Hydroxybutyrate/Acetoacetate in Biological Samples. International Journal Of Molecular Sciences 2021, 22 PMID: 33946157, PMCID: PMC8125771, DOI: 10.3390/ijms22094752.
- Goedeke L, Shulman GI. Therapeutic potential of mitochondrial uncouplers for the treatment of metabolic associated fatty liver disease and NASH. Molecular Metabolism 2021, 46: 101178. PMID: 33545391, PMCID: PMC8085597, DOI: 10.1016/j.molmet.2021.101178.
- He F, Huang Y, Song Z, Zhou HJ, Zhang H, Perry RJ, Shulman GI, Min W. Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance. The Journal Of Experimental Medicine 2021, 218 PMID: 33315085, PMCID: PMC7927432, DOI: 10.1084/jem.20201416.
- Gaspar RC, Pauli JR, Shulman GI, Muñoz VR. An update on brown adipose tissue biology: a discussion of recent findings. American Journal Of Physiology. Endocrinology And Metabolism 2021, 320: E488-E495. PMID: 33459179, PMCID: PMC7988785, DOI: 10.1152/ajpendo.00310.2020.
- Habtemichael EN, Li DT, Camporez JP, Westergaard XO, Sales CI, Liu X, López-Giráldez F, DeVries SG, Li H, Ruiz DM, Wang KY, Sayal BS, González Zapata S, Dann P, Brown SN, Hirabara S, Vatner DF, Goedeke L, Philbrick W, Shulman GI, Bogan JS. Insulin-stimulated endoproteolytic TUG cleavage links energy expenditure with glucose uptake. Nature Metabolism 2021, 3: 378-393. PMID: 33686286, PMCID: PMC7990718, DOI: 10.1038/s42255-021-00359-x.
- Lyu K, Zhang D, Song J, Li X, Perry RJ, Samuel VT, Shulman GI. Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol/PKCε/insulin receptor Thr1160 phosphorylation. JCI Insight 2021, 6 PMID: 33411692, PMCID: PMC7934919, DOI: 10.1172/jci.insight.139946.
- Hepatic Insulin Resistance Is Not Pathway Selective in Humans With Nonalcoholic Fatty Liver Disease.Ter Horst KW, Vatner DF, Zhang D, Cline GW, Ackermans MT, Nederveen AJ, Verheij J, Demirkiran A, van Wagensveld BA, Dallinga-Thie GM, Nieuwdorp M, Romijn JA, Shulman GI, Serlie MJ. Hepatic Insulin Resistance Is Not Pathway Selective in Humans With Nonalcoholic Fatty Liver Disease. Diabetes Care 2021, 44: 489-498. PMID: 33293347, PMCID: PMC7818337, DOI: 10.2337/dc20-1644.
- LaMoia TE, Shulman GI. Cellular and Molecular Mechanisms of Metformin Action. Endocrine Reviews 2021, 42: 77-96. PMID: 32897388, PMCID: PMC7846086, DOI: 10.1210/endrev/bnaa023.
- Han MS, Perry RJ, Camporez JP, Scherer PE, Shulman GI, Gao G, Davis RJ. A feed-forward regulatory loop in adipose tissue promotes signaling by the hepatokine FGF21. Genes & Development 2021, 35: 133-146. PMID: 33334822, PMCID: PMC7778269, DOI: 10.1101/gad.344556.120.
- Li X, Zhang D, Vatner DF, Goedeke L, Hirabara SM, Zhang Y, Perry RJ, Shulman GI. Mechanisms by which adiponectin reverses high fat diet-induced insulin resistance in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 32584-32593. PMID: 33293421, PMCID: PMC7768680, DOI: 10.1073/pnas.1922169117.
- Abulizi A, Vatner DF, Ye Z, Wang Y, Camporez JP, Zhang D, Kahn M, Lyu K, Sirwi A, Cline GW, Hussain MM, Aspichueta P, Samuel VT, Shulman GI. Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice. Journal Of Lipid Research 2020, 61: 1565-1576. PMID: 32907986, PMCID: PMC7707176, DOI: 10.1194/jlr.RA119000586.
- Abulizi A, Vatner DF, Ye Z, Wang Y, Camporez JP, Zhang D, Kahn M, Lyu K, Sirwi A, Cline GW, Hussain MM, Aspichueta P, Samuel VT, Shulman GI. Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice. Journal Of Lipid Research 2020, 61: 1565-1576. PMID: 33455703, DOI: 10.1194/jlr.RA119000586.
- Abulizi A, Vatner DF, Ye Z, Wang Y, Camporez JP, Zhang D, Kahn M, Lyu K, Sirwi A, Cline GW, Hussain MM, Aspichueta P, Samuel VT, Shulman GI. Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice. Journal Of Lipid Research 2020, 61: 1565-1576. PMID: 33531237, DOI: 10.1194/jlr.RA119000586.
- Song JD, Alves TC, Befroy DE, Perry RJ, Mason GF, Zhang XM, Munk A, Zhang Y, Zhang D, Cline GW, Rothman DL, Petersen KF, Shulman GI. Dissociation of Muscle Insulin Resistance from Alterations in Mitochondrial Substrate Preference. Cell Metabolism 2020, 32: 726-735.e5. PMID: 33035493, PMCID: PMC8218871, DOI: 10.1016/j.cmet.2020.09.008.
- Kahleova H, Petersen KF, Shulman GI, Alwarith J, Rembert E, Tura A, Hill M, Holubkov R, Barnard ND. Effect of a Low-Fat Vegan Diet on Body Weight, Insulin Sensitivity, Postprandial Metabolism, and Intramyocellular and Hepatocellular Lipid Levels in Overweight Adults: A Randomized Clinical Trial. JAMA Network Open 2020, 3: e2025454. PMID: 33252690, PMCID: PMC7705596, DOI: 10.1001/jamanetworkopen.2020.25454.
- Wang L, Sinnott-Armstrong N, Wagschal A, Wark AR, Camporez JP, Perry RJ, Ji F, Sohn Y, Oh J, Wu S, Chery J, Moud BN, Saadat A, Dankel SN, Mellgren G, Tallapragada DSP, Strobel SM, Lee MJ, Tewhey R, Sabeti PC, Schaefer A, Petri A, Kauppinen S, Chung RT, Soukas A, Avruch J, Fried SK, Hauner H, Sadreyev RI, Shulman GI, Claussnitzer M, Näär AM. A MicroRNA Linking Human Positive Selection and Metabolic Disorders. Cell 2020, 183: 684-701.e14. PMID: 33058756, PMCID: PMC8092355, DOI: 10.1016/j.cell.2020.09.017.
- Perry RJ, Shulman GI. Sodium-glucose cotransporter-2 inhibitors: Understanding the mechanisms for therapeutic promise and persisting risks. The Journal Of Biological Chemistry 2020, 295: 14379-14390. PMID: 32796035, PMCID: PMC7573269, DOI: 10.1074/jbc.REV120.008387.
- Lyu K, Zhang Y, Zhang D, Kahn M, Ter Horst KW, Rodrigues MRS, Gaspar RC, Hirabara SM, Luukkonen PK, Lee S, Bhanot S, Rinehart J, Blume N, Rasch MG, Serlie MJ, Bogan JS, Cline GW, Samuel VT, Shulman GI. A Membrane-Bound Diacylglycerol Species Induces PKCϵ-Mediated Hepatic Insulin Resistance. Cell Metabolism 2020, 32: 654-664.e5. PMID: 32882164, PMCID: PMC7544641, DOI: 10.1016/j.cmet.2020.08.001.
- Hall JA, Ramachandran D, Roh HC, DiSpirito JR, Belchior T, Zushin PH, Palmer C, Hong S, Mina AI, Liu B, Deng Z, Aryal P, Jacobs C, Tenen D, Brown CW, Charles JF, Shulman GI, Kahn BB, Tsai LTY, Rosen ED, Spiegelman BM, Banks AS. Obesity-Linked PPARγ S273 Phosphorylation Promotes Insulin Resistance through Growth Differentiation Factor 3. Cell Metabolism 2020, 32: 665-675.e6. PMID: 32941798, PMCID: PMC7543662, DOI: 10.1016/j.cmet.2020.08.016.
- Koh JH, Johnson ML, Dasari S, LeBrasseur NK, Vuckovic I, Henderson GC, Cooper SA, Manjunatha S, Ruegsegger GN, Shulman GI, Lanza IR, Nair KS. Erratum. TFAM Enhances Fat Oxidation and Attenuates High-Fat Diet-Induced Insulin Resistance in Skeletal Muscle. Diabetes 2019;68:1552-1564. Diabetes 2020, 69: 1854. PMID: 32532806, PMCID: PMC7519475, DOI: 10.2337/db20-er08a.
- Yang Y, Li X, Luan HH, Zhang B, Zhang K, Nam JH, Li Z, Fu M, Munk A, Zhang D, Wang S, Liu Y, Albuquerque JP, Ong Q, Li R, Wang Q, Robert ME, Perry RJ, Chung D, Shulman GI, Yang X. OGT suppresses S6K1-mediated macrophage inflammation and metabolic disturbance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 16616-16625. PMID: 32601203, PMCID: PMC7368321, DOI: 10.1073/pnas.1916121117.
- Bilet L, Phielix E, van de Weijer T, Gemmink A, Bosma M, Moonen-Kornips E, Jorgensen JA, Schaart G, Zhang D, Meijer K, Hopman M, Hesselink MKC, Ouwens DM, Shulman GI, Schrauwen-Hinderling VB, Schrauwen P. One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension. Diabetologia 2020, 63: 1211-1222. PMID: 32185462, PMCID: PMC7228997, DOI: 10.1007/s00125-020-05128-1.
- Nozaki Y, Petersen MC, Zhang D, Vatner DF, Perry RJ, Abulizi A, Haedersdal S, Zhang XM, Butrico GM, Samuel VT, Mason GF, Cline GW, Petersen KF, Rothman DL, Shulman GI. Metabolic control analysis of hepatic glycogen synthesis in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 8166-8176. PMID: 32188779, PMCID: PMC7149488, DOI: 10.1073/pnas.1921694117.
- Sangwung P, Petersen KF, Shulman GI, Knowles JW. Mitochondrial Dysfunction, Insulin Resistance, and Potential Genetic Implications. Endocrinology 2020, 161 PMID: 32060542, PMCID: PMC7341556, DOI: 10.1210/endocr/bqaa017.
- Perry RJ, Lyu K, Rabin-Court A, Dong J, Li X, Yang Y, Qing H, Wang A, Yang X, Shulman GI. Leptin mediates postprandial increases in body temperature through hypothalamus-adrenal medulla-adipose tissue crosstalk. The Journal Of Clinical Investigation 2020, 130: 2001-2016. PMID: 32149734, PMCID: PMC7108915, DOI: 10.1172/JCI134699.
- Luukkonen PK, Dufour S, Lyu K, Zhang XM, Hakkarainen A, Lehtimäki TE, Cline GW, Petersen KF, Shulman GI, Yki-Järvinen H. Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 7347-7354. PMID: 32179679, PMCID: PMC7132133, DOI: 10.1073/pnas.1922344117.
- Tarabra E, Nouws J, Vash-Margita A, Nadzam GS, Goldberg R, Van Name M, Pierpont B, Knight J, Shulman GI, Caprio S. The omentum of obese girls harbors small adipocytes and browning transcripts. JCI Insight 2020, 5 PMID: 32125283, PMCID: PMC7213797, DOI: 10.1172/jci.insight.135448.
- Perry RJ, Zhang D, Guerra MT, Brill AL, Goedeke L, Nasiri AR, Rabin-Court A, Wang Y, Peng L, Dufour S, Zhang Y, Zhang XM, Butrico GM, Toussaint K, Nozaki Y, Cline GW, Petersen KF, Nathanson MH, Ehrlich BE, Shulman GI. Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis. Nature 2020, 579: 279-283. PMID: 32132708, PMCID: PMC7101062, DOI: 10.1038/s41586-020-2074-6.
- Chande S, Caballero D, Ho BB, Fetene J, Serna J, Pesta D, Nasiri A, Jurczak M, Chavkin NW, Hernando N, Giachelli CM, Wagner CA, Zeiss C, Shulman GI, Bergwitz C. Slc20a1/Pit1 and Slc20a2/Pit2 are essential for normal skeletal myofiber function and survival. Scientific Reports 2020, 10: 3069. PMID: 32080237, PMCID: PMC7033257, DOI: 10.1038/s41598-020-59430-4.
- Han MS, White A, Perry RJ, Camporez JP, Hidalgo J, Shulman GI, Davis RJ. Regulation of adipose tissue inflammation by interleukin 6. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 2751-2760. PMID: 31980524, PMCID: PMC7022151, DOI: 10.1073/pnas.1920004117.
- Perry RJ, Shulman GI. Mechanistic Links between Obesity, Insulin, and Cancer. Trends In Cancer 2020, 6: 75-78. PMID: 32061306, PMCID: PMC7214048, DOI: 10.1016/j.trecan.2019.12.003.
- Correa-de-Araujo R, Addison O, Miljkovic I, Goodpaster BH, Bergman BC, Clark RV, Elena JW, Esser KA, Ferrucci L, Harris-Love MO, Kritchevsky SB, Lorbergs A, Shepherd JA, Shulman GI, Rosen CJ. Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging. Frontiers In Physiology 2020, 11: 963. PMID: 32903666, PMCID: PMC7438777, DOI: 10.3389/fphys.2020.00963.
- Gassaway BM, Cardone RL, Padyana AK, Petersen MC, Judd ET, Hayes S, Tong S, Barber KW, Apostolidi M, Abulizi A, Sheetz JB, Kshitiz, Aerni HR, Gross S, Kung C, Samuel VT, Shulman GI, Kibbey RG, Rinehart J. Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production. Cell Reports 2019, 29: 3394-3404.e9. PMID: 31825824, PMCID: PMC6951436, DOI: 10.1016/j.celrep.2019.11.009.
- Roden M, Shulman GI. The integrative biology of type 2 diabetes. Nature 2019, 576: 51-60. PMID: 31802013, DOI: 10.1038/s41586-019-1797-8.
- Samuel VT, Shulman GI. Nonalcoholic Fatty Liver Disease, Insulin Resistance, and Ceramides. The New England Journal Of Medicine 2019, 381: 1866-1869. PMID: 31693811, DOI: 10.1056/NEJMcibr1910023.
- Gómez-Banoy N, Guseh JS, Li G, Rubio-Navarro A, Chen T, Poirier B, Putzel G, Rosselot C, Pabón MA, Camporez JP, Bhambhani V, Hwang SJ, Yao C, Perry RJ, Mukherjee S, Larson MG, Levy D, Dow LE, Shulman GI, Dephoure N, Garcia-Ocana A, Hao M, Spiegelman BM, Ho JE, Lo JC. Adipsin preserves beta cells in diabetic mice and associates with protection from type 2 diabetes in humans. Nature Medicine 2019, 25: 1739-1747. PMID: 31700183, PMCID: PMC7256970, DOI: 10.1038/s41591-019-0610-4.
- Edmunds LR, Huckestein BR, Kahn M, Zhang D, Chu Y, Zhang Y, Wendell SG, Shulman GI, Jurczak MJ. Hepatic insulin sensitivity is improved in high-fat diet-fed Park2 knockout mice in association with increased hepatic AMPK activation and reduced steatosis. Physiological Reports 2019, 7: e14281. PMID: 31724300, PMCID: PMC6854109, DOI: 10.14814/phy2.14281.
- Goedeke L, Peng L, Montalvo-Romeral V, Butrico GM, Dufour S, Zhang XM, Perry RJ, Cline GW, Kievit P, Chng K, Petersen KF, Shulman GI. Controlled-release mitochondrial protonophore (CRMP) reverses dyslipidemia and hepatic steatosis in dysmetabolic nonhuman primates. Science Translational Medicine 2019, 11 PMID: 31578240, PMCID: PMC6996238, DOI: 10.1126/scitranslmed.aay0284.
- Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. The New England Journal Of Medicine 2014, 371: 1131-41. PMID: 25229917, DOI: 10.1056/NEJMra1011035.
- Perry RJ, Zhang XM, Zhang D, Kumashiro N, Camporez JP, Cline GW, Rothman DL, Shulman GI. Leptin reverses diabetes by suppression of the hypothalamic-pituitary-adrenal axis. Nature Medicine 2014, 20: 759-63. PMID: 24929951, PMCID: PMC4344321, DOI: 10.1038/nm.3579.
- Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, Prigaro BJ, Wood JL, Bhanot S, MacDonald MJ, Jurczak MJ, Camporez JP, Lee HY, Cline GW, Samuel VT, Kibbey RG, Shulman GI. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature 2014, 510: 542-6. PMID: 24847880, PMCID: PMC4074244, DOI: 10.1038/nature13270.
- Perry RJ, Samuel VT, Petersen KF, Shulman GI. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 2014, 510: 84-91. PMID: 24899308, PMCID: PMC4489847, DOI: 10.1038/nature13478.
- Befroy DE, Perry RJ, Jain N, Dufour S, Cline GW, Trimmer JK, Brosnan J, Rothman DL, Petersen KF, Shulman GI. Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic 13C magnetic resonance spectroscopy. Nature Medicine 2014, 20: 98-102. PMID: 24317120, PMCID: PMC3947269, DOI: 10.1038/nm.3415.
- Perry RJ, Kim T, Zhang XM, Lee HY, Pesta D, Popov VB, Zhang D, Rahimi Y, Jurczak MJ, Cline GW, Spiegel DA, Shulman GI. Reversal of hypertriglyceridemia, fatty liver disease, and insulin resistance by a liver-targeted mitochondrial uncoupler. Cell Metabolism 2013, 18: 740-8. PMID: 24206666, PMCID: PMC4104686, DOI: 10.1016/j.cmet.2013.10.004.
- Gillum MP, Zhang D, Zhang XM, Erion DM, Jamison RA, Choi C, Dong J, Shanabrough M, Duenas HR, Frederick DW, Hsiao JJ, Horvath TL, Lo CM, Tso P, Cline GW, Shulman GI. N-acylphosphatidylethanolamine, a gut- derived circulating factor induced by fat ingestion, inhibits food intake. Cell 2008, 135: 813-24. PMID: 19041747, PMCID: PMC2643061, DOI: 10.1016/j.cell.2008.10.043.
- Petersen 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: 12587-94. PMID: 17640906, PMCID: PMC1924794, DOI: 10.1073/pnas.0705408104.
- Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, Pypaert M, Shulman GI. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. The Journal Of Clinical Investigation 2005, 115: 3587-93. PMID: 16284649, PMCID: PMC1280967, DOI: 10.1172/JCI25151.
- Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. The New England Journal Of Medicine 2004, 350: 664-71. PMID: 14960743, PMCID: PMC2995502, DOI: 10.1056/NEJMoa031314.
- Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science (New York, N.Y.) 2003, 300: 1140-2. PMID: 12750520, PMCID: PMC3004429, DOI: 10.1126/science.1082889.
- Cline GW, Petersen KF, Krssak M, Shen J, Hundal RS, Trajanoski Z, Inzucchi S, Dresner A, Rothman DL, Shulman GI. Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes. The New England Journal Of Medicine 1999, 341: 240-6. PMID: 10413736, DOI: 10.1056/NEJM199907223410404.
- Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW, Slezak LA, Andersen DK, Hundal RS, Rothman DL, Petersen KF, Shulman GI. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. The Journal Of Clinical Investigation 1999, 103: 253-9. PMID: 9916137, PMCID: PMC407880, DOI: 10.1172/JCI5001.
- Rothman DL, Magnusson I, Katz LD, Shulman RG, Shulman GI. Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR. Science (New York, N.Y.) 1991, 254: 573-6. PMID: 1948033.
- Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG. Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. The New England Journal Of Medicine 1990, 322: 223-8. PMID: 2403659, DOI: 10.1056/NEJM199001253220403.
Departments and Programs
Titles
- George R. Cowgill Professor of Medicine (Endocrinology) and Professor of Cellular And Molecular Physiology
- Co-Director, Yale Diabetes Research Center, Internal Medicine
Education & Training
- Research FellowMassachusetts General Hospital/Harvard Medical School (1984)
- ResidentDuke University Medical Center (1981)
- MDWayne State University (1979)
- PhDWayne State University, Physiology (1979)
Additional Information
Honors & Recognitions
- Manpei Suzuki International Prize for Diabetes Research: Manpei Suzuki Diabetes Foundation (2021)
- Elected to Fellowship in the Royal College of Physicians: Royal College of Physicians (London) (2021)
- Elected to Mastership, American College of Physicians: American College of Physicians (2020)
- Samuel Eichold II Memorial Award for Contributions in Diabetes: American College of Physicians (2020)
- Arthur Riggs Award for Discoveries in the Basic Sciences: City of Hope (2019)
- Stanley Mirsky Award: Ichan School of Medicine (2019)
- Banting Medal for Scientific Achievement: American Diabetes Association (2018)
- Elected to the American Academy of Arts & Sciences: American Academy of Arts & Sciences (2018)
- Special Achievement Award: The Miami Winter Symposium (2017)
- Guyton Distinguished Visiting Professor Award: University of Mississippi (2017)
Board Certifications
- AB of Internal Medicine, Endocrinology & Metabolism (1985, recertified: 1985)
- AB of Internal Medicine, Internal Medicine (1982)
Professional Service
- Proceedings of the National Academy of Sciences (2021 - 2022): Member of the Editorial Board
- Science Translational Medicine (2013 - Present): Member of Editorial Board/Advisory Board
- Clinical and Translational Science (2008 - Present): Member of Editorial Board
- Cell Metabolism (2004 - Present): Member of Editorial Board
- Journal of Biological Chemistry (2002 - 2008): Member of Editorial Board
- American Journal of Physiology, Endocrinology/Metabolism (2001 - 2007): Member of Editorial Board
- Current Diabetes Reports (2001 - Present): Member of Editorial Board
- Journal of Clinical Investigation (1998 - Present): Member of Editorial Board
- International Journal of Molecular Medicine (1997 - 2005): Member of Editorial Board
- Diabetologia (1997 - 2001): Member of Editorial Board
Publications
- Huang Y, Zhou JH, Zhang H, Canfran-Duque A, Singh AK, Perry RJ, Shulman G, Fernandez-Hernando C, Min W. Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance. The Journal Of Clinical Investigation 2022, 132 PMID: 35202005, PMCID: PMC9057632, DOI: 10.1172/JCI148852.
- DeVito LM, Dennis EA, Kahn BB, Shulman GI, Witztum JL, Sadhu S, Nickels J, Spite M, Smyth S, Spiegel S. Bioactive lipids and metabolic syndrome-a symposium report. Annals Of The New York Academy Of Sciences 2022, 1511: 87-106. PMID: 35218041, PMCID: PMC9219555, DOI: 10.1111/nyas.14752.
- Petersen KF, Dufour S, Li F, Rothman DL, Shulman GI. Ethnic and sex differences in hepatic lipid content and related cardiometabolic parameters in lean individuals. JCI Insight 2022, 7 PMID: 35167495, PMCID: PMC9057590, DOI: 10.1172/jci.insight.157906.
- LaMoia TE, Butrico GM, Kalpage HA, Goedeke L, Hubbard BT, Vatner DF, Gaspar RC, Zhang XM, Cline GW, Nakahara K, Woo S, Shimada A, Hüttemann M, Shulman GI. Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2122287119. PMID: 35238637, PMCID: PMC8916010, DOI: 10.1073/pnas.2122287119.
- Bhat N, Narayanan A, Fathzadeh M, Kahn M, Zhang D, Goedeke L, Neogi A, Cardone RL, Kibbey RG, Fernandez-Hernando C, Ginsberg HN, Jain D, Shulman G, Mani A. Dyrk1b promotes hepatic lipogenesis by bypassing canonical insulin signaling and directly activating mTORC2 in mice. The Journal Of Clinical Investigation 2022, 132 PMID: 34855620, PMCID: PMC8803348, DOI: 10.1172/JCI153724.
- Goedeke L, Murt KN, Di Francesco A, Camporez JP, Nasiri AR, Wang Y, Zhang XM, Cline GW, de Cabo R, Shulman GI. Sex- and strain-specific effects of mitochondrial uncoupling on age-related metabolic diseases in high-fat diet-fed mice. Aging Cell 2022, 21: e13539. PMID: 35088525, PMCID: PMC8844126, DOI: 10.1111/acel.13539.
- Tarabra E, Nouws J, Vash-Margita A, Hellerstein M, Shabanova V, McCollum S, Pierpont B, Zhao D, Shulman GI, Caprio S. CIDEA expression in SAT from adolescent girls with obesity and unfavorable patterns of abdominal fat distribution. Obesity (Silver Spring, Md.) 2021, 29: 2068-2080. PMID: 34672413, PMCID: PMC8612981, DOI: 10.1002/oby.23295.
- Wang Q, Li D, Cao G, Shi Q, Zhu J, Zhang M, Cheng H, Wen Q, Xu H, Zhu L, Zhang H, Perry RJ, Spadaro O, Yang Y, He S, Chen Y, Wang B, Li G, Liu Z, Yang C, Wu X, Zhou L, Zhou Q, Ju Z, Lu H, Xin Y, Yang X, Wang C, Liu Y, Shulman GI, Dixit VD, Lu L, Yang H, Flavell RA, Yin Z. IL-27 signalling promotes adipocyte thermogenesis and energy expenditure. Nature 2021, 600: 314-318. PMID: 34819664, DOI: 10.1038/s41586-021-04127-5.
- Goedeke L, Canfrán-Duque A, Rotllan N, Chaube B, Thompson BM, Lee RG, Cline GW, McDonald JG, Shulman GI, Lasunción MA, Suárez Y, Fernández-Hernando C. MMAB promotes negative feedback control of cholesterol homeostasis. Nature Communications 2021, 12: 6448. PMID: 34750386, PMCID: PMC8575900, DOI: 10.1038/s41467-021-26787-7.
- Jiang Z, Zhao M, Voilquin L, Jung Y, Aikio MA, Sahai T, Dou FY, Roche AM, Carcamo-Orive I, Knowles JW, Wabitsch M, Appel EA, Maikawa CL, Camporez JP, Shulman GI, Tsai L, Rosen ED, Gardner CD, Spiegelman BM, Svensson KJ. Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis. Cell Metabolism 2021, 33: 1836-1852.e11. PMID: 34348115, PMCID: PMC8429235, DOI: 10.1016/j.cmet.2021.07.010.
- Schumann T, König J, von Loeffelholz C, Vatner DF, Zhang D, Perry RJ, Bernier M, Chami J, Henke C, Kurzbach A, El-Agroudy NN, Willmes DM, Pesta D, de Cabo R, O Sullivan JF, Simon E, Shulman GI, Hamilton BS, Birkenfeld AL. Publisher Correction: Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance. Communications Biology 2021, 4: 890. PMID: 34262128, PMCID: PMC8280181, DOI: 10.1038/s42003-021-02425-2.
- Schumann T, König J, von Loeffelholz C, Vatner DF, Zhang D, Perry RJ, Bernier M, Chami J, Henke C, Kurzbach A, El-Agroudy NN, Willmes DM, Pesta D, de Cabo R, O Sullivan JF, Simon E, Shulman GI, Hamilton BS, Birkenfeld AL. Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance. Communications Biology 2021, 4: 826. PMID: 34211098, PMCID: PMC8249653, DOI: 10.1038/s42003-021-02279-8.
- Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell 2021, 184: 2537-2564. PMID: 33989548, DOI: 10.1016/j.cell.2021.04.015.
- Petersen KF, Rothman D, Shulman GI. Reply to Carter et al.: An alternative hypothesis for why exposure to static magnetic and electric fields treats type 2 diabetes. American Journal Of Physiology. Endocrinology And Metabolism 2021, 320: E1003. PMID: 33843277, DOI: 10.1152/ajpendo.00120.2021.
- Petersen KF, Rothman D, Shulman GI. Point: An alternative hypothesis for why exposure to static magnetic and electric fields treats type 2 diabetes. American Journal Of Physiology. Endocrinology And Metabolism 2021, 320: E999-E1000. PMID: 33843279, DOI: 10.1152/ajpendo.00657.2020.
- Wijngaard R, Perramón M, Parra-Robert M, Hidalgo S, Butrico G, Morales-Ruiz M, Zeng M, Casals E, Jiménez W, Fernández-Varo G, Shulman GI, Cline GW, Casals G. Validation of a Gas Chromatography-Mass Spectrometry Method for the Measurement of the Redox State Metabolic Ratios Lactate/Pyruvate and β-Hydroxybutyrate/Acetoacetate in Biological Samples. International Journal Of Molecular Sciences 2021, 22 PMID: 33946157, PMCID: PMC8125771, DOI: 10.3390/ijms22094752.
- Goedeke L, Shulman GI. Therapeutic potential of mitochondrial uncouplers for the treatment of metabolic associated fatty liver disease and NASH. Molecular Metabolism 2021, 46: 101178. PMID: 33545391, PMCID: PMC8085597, DOI: 10.1016/j.molmet.2021.101178.
- He F, Huang Y, Song Z, Zhou HJ, Zhang H, Perry RJ, Shulman GI, Min W. Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance. The Journal Of Experimental Medicine 2021, 218 PMID: 33315085, PMCID: PMC7927432, DOI: 10.1084/jem.20201416.
- Gaspar RC, Pauli JR, Shulman GI, Muñoz VR. An update on brown adipose tissue biology: a discussion of recent findings. American Journal Of Physiology. Endocrinology And Metabolism 2021, 320: E488-E495. PMID: 33459179, PMCID: PMC7988785, DOI: 10.1152/ajpendo.00310.2020.
- Habtemichael EN, Li DT, Camporez JP, Westergaard XO, Sales CI, Liu X, López-Giráldez F, DeVries SG, Li H, Ruiz DM, Wang KY, Sayal BS, González Zapata S, Dann P, Brown SN, Hirabara S, Vatner DF, Goedeke L, Philbrick W, Shulman GI, Bogan JS. Insulin-stimulated endoproteolytic TUG cleavage links energy expenditure with glucose uptake. Nature Metabolism 2021, 3: 378-393. PMID: 33686286, PMCID: PMC7990718, DOI: 10.1038/s42255-021-00359-x.
- Lyu K, Zhang D, Song J, Li X, Perry RJ, Samuel VT, Shulman GI. Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol/PKCε/insulin receptor Thr1160 phosphorylation. JCI Insight 2021, 6 PMID: 33411692, PMCID: PMC7934919, DOI: 10.1172/jci.insight.139946.
- Hepatic Insulin Resistance Is Not Pathway Selective in Humans With Nonalcoholic Fatty Liver Disease.Ter Horst KW, Vatner DF, Zhang D, Cline GW, Ackermans MT, Nederveen AJ, Verheij J, Demirkiran A, van Wagensveld BA, Dallinga-Thie GM, Nieuwdorp M, Romijn JA, Shulman GI, Serlie MJ. Hepatic Insulin Resistance Is Not Pathway Selective in Humans With Nonalcoholic Fatty Liver Disease. Diabetes Care 2021, 44: 489-498. PMID: 33293347, PMCID: PMC7818337, DOI: 10.2337/dc20-1644.
- LaMoia TE, Shulman GI. Cellular and Molecular Mechanisms of Metformin Action. Endocrine Reviews 2021, 42: 77-96. PMID: 32897388, PMCID: PMC7846086, DOI: 10.1210/endrev/bnaa023.
- Han MS, Perry RJ, Camporez JP, Scherer PE, Shulman GI, Gao G, Davis RJ. A feed-forward regulatory loop in adipose tissue promotes signaling by the hepatokine FGF21. Genes & Development 2021, 35: 133-146. PMID: 33334822, PMCID: PMC7778269, DOI: 10.1101/gad.344556.120.
- Li X, Zhang D, Vatner DF, Goedeke L, Hirabara SM, Zhang Y, Perry RJ, Shulman GI. Mechanisms by which adiponectin reverses high fat diet-induced insulin resistance in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 32584-32593. PMID: 33293421, PMCID: PMC7768680, DOI: 10.1073/pnas.1922169117.
- Abulizi A, Vatner DF, Ye Z, Wang Y, Camporez JP, Zhang D, Kahn M, Lyu K, Sirwi A, Cline GW, Hussain MM, Aspichueta P, Samuel VT, Shulman GI. Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice. Journal Of Lipid Research 2020, 61: 1565-1576. PMID: 32907986, PMCID: PMC7707176, DOI: 10.1194/jlr.RA119000586.
- Abulizi A, Vatner DF, Ye Z, Wang Y, Camporez JP, Zhang D, Kahn M, Lyu K, Sirwi A, Cline GW, Hussain MM, Aspichueta P, Samuel VT, Shulman GI. Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice. Journal Of Lipid Research 2020, 61: 1565-1576. PMID: 33455703, DOI: 10.1194/jlr.RA119000586.
- Abulizi A, Vatner DF, Ye Z, Wang Y, Camporez JP, Zhang D, Kahn M, Lyu K, Sirwi A, Cline GW, Hussain MM, Aspichueta P, Samuel VT, Shulman GI. Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice. Journal Of Lipid Research 2020, 61: 1565-1576. PMID: 33531237, DOI: 10.1194/jlr.RA119000586.
- Song JD, Alves TC, Befroy DE, Perry RJ, Mason GF, Zhang XM, Munk A, Zhang Y, Zhang D, Cline GW, Rothman DL, Petersen KF, Shulman GI. Dissociation of Muscle Insulin Resistance from Alterations in Mitochondrial Substrate Preference. Cell Metabolism 2020, 32: 726-735.e5. PMID: 33035493, PMCID: PMC8218871, DOI: 10.1016/j.cmet.2020.09.008.
- Kahleova H, Petersen KF, Shulman GI, Alwarith J, Rembert E, Tura A, Hill M, Holubkov R, Barnard ND. Effect of a Low-Fat Vegan Diet on Body Weight, Insulin Sensitivity, Postprandial Metabolism, and Intramyocellular and Hepatocellular Lipid Levels in Overweight Adults: A Randomized Clinical Trial. JAMA Network Open 2020, 3: e2025454. PMID: 33252690, PMCID: PMC7705596, DOI: 10.1001/jamanetworkopen.2020.25454.
- Wang L, Sinnott-Armstrong N, Wagschal A, Wark AR, Camporez JP, Perry RJ, Ji F, Sohn Y, Oh J, Wu S, Chery J, Moud BN, Saadat A, Dankel SN, Mellgren G, Tallapragada DSP, Strobel SM, Lee MJ, Tewhey R, Sabeti PC, Schaefer A, Petri A, Kauppinen S, Chung RT, Soukas A, Avruch J, Fried SK, Hauner H, Sadreyev RI, Shulman GI, Claussnitzer M, Näär AM. A MicroRNA Linking Human Positive Selection and Metabolic Disorders. Cell 2020, 183: 684-701.e14. PMID: 33058756, PMCID: PMC8092355, DOI: 10.1016/j.cell.2020.09.017.
- Perry RJ, Shulman GI. Sodium-glucose cotransporter-2 inhibitors: Understanding the mechanisms for therapeutic promise and persisting risks. The Journal Of Biological Chemistry 2020, 295: 14379-14390. PMID: 32796035, PMCID: PMC7573269, DOI: 10.1074/jbc.REV120.008387.
- Lyu K, Zhang Y, Zhang D, Kahn M, Ter Horst KW, Rodrigues MRS, Gaspar RC, Hirabara SM, Luukkonen PK, Lee S, Bhanot S, Rinehart J, Blume N, Rasch MG, Serlie MJ, Bogan JS, Cline GW, Samuel VT, Shulman GI. A Membrane-Bound Diacylglycerol Species Induces PKCϵ-Mediated Hepatic Insulin Resistance. Cell Metabolism 2020, 32: 654-664.e5. PMID: 32882164, PMCID: PMC7544641, DOI: 10.1016/j.cmet.2020.08.001.
- Hall JA, Ramachandran D, Roh HC, DiSpirito JR, Belchior T, Zushin PH, Palmer C, Hong S, Mina AI, Liu B, Deng Z, Aryal P, Jacobs C, Tenen D, Brown CW, Charles JF, Shulman GI, Kahn BB, Tsai LTY, Rosen ED, Spiegelman BM, Banks AS. Obesity-Linked PPARγ S273 Phosphorylation Promotes Insulin Resistance through Growth Differentiation Factor 3. Cell Metabolism 2020, 32: 665-675.e6. PMID: 32941798, PMCID: PMC7543662, DOI: 10.1016/j.cmet.2020.08.016.
- Koh JH, Johnson ML, Dasari S, LeBrasseur NK, Vuckovic I, Henderson GC, Cooper SA, Manjunatha S, Ruegsegger GN, Shulman GI, Lanza IR, Nair KS. Erratum. TFAM Enhances Fat Oxidation and Attenuates High-Fat Diet-Induced Insulin Resistance in Skeletal Muscle. Diabetes 2019;68:1552-1564. Diabetes 2020, 69: 1854. PMID: 32532806, PMCID: PMC7519475, DOI: 10.2337/db20-er08a.
- Yang Y, Li X, Luan HH, Zhang B, Zhang K, Nam JH, Li Z, Fu M, Munk A, Zhang D, Wang S, Liu Y, Albuquerque JP, Ong Q, Li R, Wang Q, Robert ME, Perry RJ, Chung D, Shulman GI, Yang X. OGT suppresses S6K1-mediated macrophage inflammation and metabolic disturbance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 16616-16625. PMID: 32601203, PMCID: PMC7368321, DOI: 10.1073/pnas.1916121117.
- Bilet L, Phielix E, van de Weijer T, Gemmink A, Bosma M, Moonen-Kornips E, Jorgensen JA, Schaart G, Zhang D, Meijer K, Hopman M, Hesselink MKC, Ouwens DM, Shulman GI, Schrauwen-Hinderling VB, Schrauwen P. One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension. Diabetologia 2020, 63: 1211-1222. PMID: 32185462, PMCID: PMC7228997, DOI: 10.1007/s00125-020-05128-1.
- Nozaki Y, Petersen MC, Zhang D, Vatner DF, Perry RJ, Abulizi A, Haedersdal S, Zhang XM, Butrico GM, Samuel VT, Mason GF, Cline GW, Petersen KF, Rothman DL, Shulman GI. Metabolic control analysis of hepatic glycogen synthesis in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 8166-8176. PMID: 32188779, PMCID: PMC7149488, DOI: 10.1073/pnas.1921694117.
- Sangwung P, Petersen KF, Shulman GI, Knowles JW. Mitochondrial Dysfunction, Insulin Resistance, and Potential Genetic Implications. Endocrinology 2020, 161 PMID: 32060542, PMCID: PMC7341556, DOI: 10.1210/endocr/bqaa017.
- Perry RJ, Lyu K, Rabin-Court A, Dong J, Li X, Yang Y, Qing H, Wang A, Yang X, Shulman GI. Leptin mediates postprandial increases in body temperature through hypothalamus-adrenal medulla-adipose tissue crosstalk. The Journal Of Clinical Investigation 2020, 130: 2001-2016. PMID: 32149734, PMCID: PMC7108915, DOI: 10.1172/JCI134699.
- Luukkonen PK, Dufour S, Lyu K, Zhang XM, Hakkarainen A, Lehtimäki TE, Cline GW, Petersen KF, Shulman GI, Yki-Järvinen H. Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 7347-7354. PMID: 32179679, PMCID: PMC7132133, DOI: 10.1073/pnas.1922344117.
- Tarabra E, Nouws J, Vash-Margita A, Nadzam GS, Goldberg R, Van Name M, Pierpont B, Knight J, Shulman GI, Caprio S. The omentum of obese girls harbors small adipocytes and browning transcripts. JCI Insight 2020, 5 PMID: 32125283, PMCID: PMC7213797, DOI: 10.1172/jci.insight.135448.
- Perry RJ, Zhang D, Guerra MT, Brill AL, Goedeke L, Nasiri AR, Rabin-Court A, Wang Y, Peng L, Dufour S, Zhang Y, Zhang XM, Butrico GM, Toussaint K, Nozaki Y, Cline GW, Petersen KF, Nathanson MH, Ehrlich BE, Shulman GI. Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis. Nature 2020, 579: 279-283. PMID: 32132708, PMCID: PMC7101062, DOI: 10.1038/s41586-020-2074-6.
- Chande S, Caballero D, Ho BB, Fetene J, Serna J, Pesta D, Nasiri A, Jurczak M, Chavkin NW, Hernando N, Giachelli CM, Wagner CA, Zeiss C, Shulman GI, Bergwitz C. Slc20a1/Pit1 and Slc20a2/Pit2 are essential for normal skeletal myofiber function and survival. Scientific Reports 2020, 10: 3069. PMID: 32080237, PMCID: PMC7033257, DOI: 10.1038/s41598-020-59430-4.
- Han MS, White A, Perry RJ, Camporez JP, Hidalgo J, Shulman GI, Davis RJ. Regulation of adipose tissue inflammation by interleukin 6. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 2751-2760. PMID: 31980524, PMCID: PMC7022151, DOI: 10.1073/pnas.1920004117.
- Perry RJ, Shulman GI. Mechanistic Links between Obesity, Insulin, and Cancer. Trends In Cancer 2020, 6: 75-78. PMID: 32061306, PMCID: PMC7214048, DOI: 10.1016/j.trecan.2019.12.003.
- Correa-de-Araujo R, Addison O, Miljkovic I, Goodpaster BH, Bergman BC, Clark RV, Elena JW, Esser KA, Ferrucci L, Harris-Love MO, Kritchevsky SB, Lorbergs A, Shepherd JA, Shulman GI, Rosen CJ. Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging. Frontiers In Physiology 2020, 11: 963. PMID: 32903666, PMCID: PMC7438777, DOI: 10.3389/fphys.2020.00963.
- Gassaway BM, Cardone RL, Padyana AK, Petersen MC, Judd ET, Hayes S, Tong S, Barber KW, Apostolidi M, Abulizi A, Sheetz JB, Kshitiz, Aerni HR, Gross S, Kung C, Samuel VT, Shulman GI, Kibbey RG, Rinehart J. Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production. Cell Reports 2019, 29: 3394-3404.e9. PMID: 31825824, PMCID: PMC6951436, DOI: 10.1016/j.celrep.2019.11.009.
- Roden M, Shulman GI. The integrative biology of type 2 diabetes. Nature 2019, 576: 51-60. PMID: 31802013, DOI: 10.1038/s41586-019-1797-8.
- Samuel VT, Shulman GI. Nonalcoholic Fatty Liver Disease, Insulin Resistance, and Ceramides. The New England Journal Of Medicine 2019, 381: 1866-1869. PMID: 31693811, DOI: 10.1056/NEJMcibr1910023.
- Gómez-Banoy N, Guseh JS, Li G, Rubio-Navarro A, Chen T, Poirier B, Putzel G, Rosselot C, Pabón MA, Camporez JP, Bhambhani V, Hwang SJ, Yao C, Perry RJ, Mukherjee S, Larson MG, Levy D, Dow LE, Shulman GI, Dephoure N, Garcia-Ocana A, Hao M, Spiegelman BM, Ho JE, Lo JC. Adipsin preserves beta cells in diabetic mice and associates with protection from type 2 diabetes in humans. Nature Medicine 2019, 25: 1739-1747. PMID: 31700183, PMCID: PMC7256970, DOI: 10.1038/s41591-019-0610-4.
- Edmunds LR, Huckestein BR, Kahn M, Zhang D, Chu Y, Zhang Y, Wendell SG, Shulman GI, Jurczak MJ. Hepatic insulin sensitivity is improved in high-fat diet-fed Park2 knockout mice in association with increased hepatic AMPK activation and reduced steatosis. Physiological Reports 2019, 7: e14281. PMID: 31724300, PMCID: PMC6854109, DOI: 10.14814/phy2.14281.
- Goedeke L, Peng L, Montalvo-Romeral V, Butrico GM, Dufour S, Zhang XM, Perry RJ, Cline GW, Kievit P, Chng K, Petersen KF, Shulman GI. Controlled-release mitochondrial protonophore (CRMP) reverses dyslipidemia and hepatic steatosis in dysmetabolic nonhuman primates. Science Translational Medicine 2019, 11 PMID: 31578240, PMCID: PMC6996238, DOI: 10.1126/scitranslmed.aay0284.
- Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. The New England Journal Of Medicine 2014, 371: 1131-41. PMID: 25229917, DOI: 10.1056/NEJMra1011035.
- Perry RJ, Zhang XM, Zhang D, Kumashiro N, Camporez JP, Cline GW, Rothman DL, Shulman GI. Leptin reverses diabetes by suppression of the hypothalamic-pituitary-adrenal axis. Nature Medicine 2014, 20: 759-63. PMID: 24929951, PMCID: PMC4344321, DOI: 10.1038/nm.3579.
- Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, Prigaro BJ, Wood JL, Bhanot S, MacDonald MJ, Jurczak MJ, Camporez JP, Lee HY, Cline GW, Samuel VT, Kibbey RG, Shulman GI. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature 2014, 510: 542-6. PMID: 24847880, PMCID: PMC4074244, DOI: 10.1038/nature13270.
- Perry RJ, Samuel VT, Petersen KF, Shulman GI. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 2014, 510: 84-91. PMID: 24899308, PMCID: PMC4489847, DOI: 10.1038/nature13478.
- Befroy DE, Perry RJ, Jain N, Dufour S, Cline GW, Trimmer JK, Brosnan J, Rothman DL, Petersen KF, Shulman GI. Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic 13C magnetic resonance spectroscopy. Nature Medicine 2014, 20: 98-102. PMID: 24317120, PMCID: PMC3947269, DOI: 10.1038/nm.3415.
- Perry RJ, Kim T, Zhang XM, Lee HY, Pesta D, Popov VB, Zhang D, Rahimi Y, Jurczak MJ, Cline GW, Spiegel DA, Shulman GI. Reversal of hypertriglyceridemia, fatty liver disease, and insulin resistance by a liver-targeted mitochondrial uncoupler. Cell Metabolism 2013, 18: 740-8. PMID: 24206666, PMCID: PMC4104686, DOI: 10.1016/j.cmet.2013.10.004.
- Gillum MP, Zhang D, Zhang XM, Erion DM, Jamison RA, Choi C, Dong J, Shanabrough M, Duenas HR, Frederick DW, Hsiao JJ, Horvath TL, Lo CM, Tso P, Cline GW, Shulman GI. N-acylphosphatidylethanolamine, a gut- derived circulating factor induced by fat ingestion, inhibits food intake. Cell 2008, 135: 813-24. PMID: 19041747, PMCID: PMC2643061, DOI: 10.1016/j.cell.2008.10.043.
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- Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. The New England Journal Of Medicine 2004, 350: 664-71. PMID: 14960743, PMCID: PMC2995502, DOI: 10.1056/NEJMoa031314.
- Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science (New York, N.Y.) 2003, 300: 1140-2. PMID: 12750520, PMCID: PMC3004429, DOI: 10.1126/science.1082889.
- Cline GW, Petersen KF, Krssak M, Shen J, Hundal RS, Trajanoski Z, Inzucchi S, Dresner A, Rothman DL, Shulman GI. Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes. The New England Journal Of Medicine 1999, 341: 240-6. PMID: 10413736, DOI: 10.1056/NEJM199907223410404.
- Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW, Slezak LA, Andersen DK, Hundal RS, Rothman DL, Petersen KF, Shulman GI. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. The Journal Of Clinical Investigation 1999, 103: 253-9. PMID: 9916137, PMCID: PMC407880, DOI: 10.1172/JCI5001.
- Rothman DL, Magnusson I, Katz LD, Shulman RG, Shulman GI. Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR. Science (New York, N.Y.) 1991, 254: 573-6. PMID: 1948033.
- Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG. Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. The New England Journal Of Medicine 1990, 322: 223-8. PMID: 2403659, DOI: 10.1056/NEJM199001253220403.
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