Mechanisms of insulin resistance in humans and possible links with inflammation

Hypertension. 2005 May;45(5):828-33. doi: 10.1161/01.HYP.0000163475.04421.e4. Epub 2005 Apr 11.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Fatty Acids / metabolism
  • Glucose / metabolism
  • Humans
  • Inflammation / etiology*
  • Insulin Resistance / physiology*
  • Lipid Metabolism
  • Liver / metabolism
  • Muscle, Skeletal / metabolism
  • Obesity / complications
  • Obesity / physiopathology

Substances

  • Fatty Acids
  • Glucose