Gerald I Shulman, MD, PhD, FACP, FACE

George R. Cowgill Professor of Medicine (Endocrinology) and Professor of Cellular and Molecular Physiology; Investigator, Howard Hughes Medical Institute; Co-Director, Yale Diabetes Research Center; Director, Yale Mouse Metabolic Phenotyping Center

Research Interests

Endocrine System Diseases; Chemicals and Drugs; Analytical, Diagnostic and Therapeutic Techniques and Equipment

Research Organizations

Cellular & Molecular Physiology: Epithelial Transport of Ions and Solutes | Organ Physiology | Physiology of Human Disease

Center for X-Linked Hypophosphatemia, Yale

Internal Medicine: Diabetes Research Center | Endocrinology: Fellowship Training

Mouse Metabolic Phenotyping Center

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.

Selected Publications

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