Hypertension. 2005;45:828-833
Published online before print April 11, 2005, doi: 10.1161/01.HYP.0000163475.04421.e4
Published online before print April 11, 2005, doi: 10.1161/01.HYP.0000163475.04421.e4
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(Hypertension. 2005;45:828.)
© 2005 American Heart Association, Inc.
Brief Review |
Mechanisms of Insulin Resistance in Humans and Possible Links With Inflammation
From the Departments of Internal Medicine (D.B.S., K.F.P., G.I.S.) and Cellular and Molecular Physiology (G.I.S.), Howard Hughes Medical Institute (G.I.S.), Yale University School of Medicine, New Haven, Conn.
Correspondence to Gerald I. Shulman, MD, PhD, TAC S269, PO Box 9012, 300 Cedar St, Yale University School of Medicine, New Haven, CT 06510. E-mail gerald.shulman{at}yale.edu
Insulin resistance is a major player in the pathogenesis of the metabolic syndrome and type 2 diabetes, and yet, the mechanisms responsible for it remain poorly understood. Magnetic resonance spectroscopy studies in humans suggest that a defect in insulin-stimulated glucose transport in skeletal muscle is the primary metabolic abnormality in insulin-resistant type 2 diabetics. Fatty acids appear to cause this defect in glucose transport by inhibiting insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1 associated phosphatidylinositol 3-kinase activity. A number of different metabolic abnormalities may increase intramyocellular/intrahepatic fatty acid metabolites; these include increased fat delivery to muscle/liver as a consequence of either excess energy intake or defects in adipocyte fat metabolism and acquired or inherited defects in mitochondrial fatty acid oxidation. Understanding the molecular/biochemical defects responsible for insulin resistance is beginning to unveil novel therapeutic targets for treatment of the metabolic syndrome and type 2 diabetes.
Key Words: insulin resistance • fatty acids
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