Scientific Director Gerald I. Shulman – University of Copenhagen

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Novo Nordisk Foundation Center for Basic Metabolic Research > Research > Section for Metabolic Imaging and Liver Metabolism > Metabolic Imaging and Liver Metabolism staff > Scientific Director Ge...

Scientific Director Gerald I. Shulman

MD, DMSc, Professor 

Curriculum in Brief

Dr. Shulman is the George R. Cowgill Professor of Physiological Chemistry, Medicine and Cellular & Molecular Physiology at Yale University as well as an Investigator of the Howard Hughes Medical Institute. He is also Associate Director of the Yale Diabetes-Endocrinology Research Center and Associate Director of the Yale Medical Scientist Training Program.

Dr. Shulman has pioneered the use of magnetic resonance spectroscopy (MRS) to non-invasively examine intracellular glucose and fat metabolism in humans.

Awards and Honors

Dr. Shulmans work has been recognized with numerous honors and awards including the Outstanding Investigator Award from the American Federation for Clinical Research, the Diabetes Care Research Award from the Juvenile Diabetes Research Foundation, the Novartis Award in Diabetes, the Outstanding Scientific Achievement Award and the Distinguished Clinical Scientist Award from the American Diabetes Association and the Stanley J. Korsmeyer Award from the American Society for Clinical Investigation.

Dr. Shulman has been elected to the Association of American Physicians, Fellow of the American Association for the Advancement of Science, the Institute of Medicine and the National Academy of Sciences.

Research profile

Using NMR spectroscopy his group found that decreased insulin-stimulated muscle glycogen synthesis, due to defects in insulin stimulated glucose transport, is the major factor responsible for peripheral insulin resistance and that increased hepatic gluconeogenesis is responsible for fasting hyperglycemia in T2D.

His group then went on to demonstrate that fatty acids induced insulin resistance through a reduction in insulin stimulated muscle glycogen synthesis, which could be attributed to reduced glucose transport activity due a block in insulin signaling.
These results led him to propose a unifying hypothesis for insulin resistance, which postulates that an increase in intracellular diacylglycerol, due to an imbalance between fatty acid delivery versus fatty acid oxidation/storage, causes insulin resistance by activation of a serine kinase cascade involving nPKCs leading to inhibition of insulin signaling at the level of IRS-1 tyrosine phosphorylation.

His group has also found that a similar mechanism causes hepatic insulin resistance associated with non alcoholic fatty liver disease (NAFLD) and that NAFLD and hepatic insulin resistance can be reversed with modest weight reduction in T2D or with leptin replacement in lipodystrophy.

Most recently his group has identified a common polymorphism in apolipoprotein C3, which predisposes individuals to NAFLD and insulin resistance.

Key Recent Discoveries

N-cylphosphatidylethanolamine, a Gut-Derived Circulating Factor Induced by Fat Ingestion
Identified a novel gut-derived phospholipid that regulates food intake.
Ref: Gillum, M, Zhang, D, Zhang, X-M, Erion, D, Jamison, R, Choi, C, Dong, J, Shanabrough, M, Duenas, H, Frederick, D, Hsiao, J, Horvath, T, Lo, C, Tso, P, Cline, G, Shulman, GI. Inhibits Food Intake.
Cell 2008:135;813-824.

Apolipoprotein C3 Gene Variants Promote Non-Alcoholic Fatty Liver Disease and Insulin Resistance
Identified common gene variants in Apo C3, which predispose individuals to NAFLD and hepatic insulin resistance and delineated the mechanism by which they do so.
Ref: Petersen, KF, Dufour, S, Hariri, A, Nelson-Williams, C, Foo, J, Zhang, XM, Dziura, J, Lifton, R, and Shulman, GI. N Engl J Med 2010;362:1082-9.