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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

Despite much work the cellular mechanisms responsible for insulin resistance in type 2 diabetes and the metabolic syndrome remain unknown. In this regard recent studies measuring muscle triglyceride content by biopsy or intramyocellular lipid content by 1H magnetic resonance spectroscopy have shown a strong relationship between intramuscular lipid content and insulin resistance in skeletal muscle. Recent studies have also demonstrated increases in intramyocellular lipid content in insulin resistant offspring of parents with type 2 diabetes suggesting that dysregulation of fatty acid metabolism may be responsible for mediating the insulin resistance in these individuals. Increases in the intramyocellular concentration of fatty acid metabolites in turn have been postulated to activate a serine kinase cascade leading to decreased insulin stimulated insulin receptor substrate-1 associated phosphatidylinositol 3-kinase activity resulting in reduced glucose transport activity and glycogen synthesis. This presentation will focus on recent studies using noninvasive 13C, 31P and 1H magnetic resonance spectroscopy techniques in humans that elucidate the pathogenesis of insulin resistance that occurs in obesity, type 2 diabetes, lipodystrophy and the metabolic syndrome.

Extensive Research Description

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

Coauthors

Research Interests

Endocrine System Diseases; Insulin Resistance; 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