OUP user menu

Role of fatty acids in the development of insulin resistance and type 2 diabetes mellitus

George Wolf
DOI: http://dx.doi.org/10.1111/j.1753-4887.2008.00110.x 597-600 First published online: 1 October 2008


Insulin resistance is defined as the reduced responsiveness to normal circulating levels of insulin. It is the basic condition of type 2 diabetes mellitus, in which both experimental animals and humans accumulate lipids intracellularly in skeletal muscle and liver. Measurement of these lipids in humans, using nuclear magnetic resonance spectroscopy after lipid infusion, indicated they could cause inhibition of the glucose transporter GLUT4, thereby suppressing glucose entry into cells and inhibiting glucose oxidation and glycogen synthesis in muscle. Furthermore, it is known that the enzyme acetyl-CoA carboxylase2 (ACC2) suppresses the oxidation of fatty acids by inhibiting the entry of fatty acids into mitochondria. Further support for the lipocentric hypothesis of the pathogenesis of insulin resistance was provided by knocking out the gene coding for ACC2 in mice; this led to greater fatty acid oxidation, reduced fat mass and, in consequence, greatly enhanced insulin sensitivity. These studies suggest that a specific inhibitor of ACC2 would have therapeutic potential for type 2 diabetes mellitus.

  • acetyl-CoA carboxylase2 knockout mouse
  • Akt2
  • diacylglycerol
  • GLUT4
  • nuclear magnetic resonance spectroscopy
View Full Text

Sign in

Log in through your institution

Sign in as a personal subscriber

Log in through your institution

Purchase a personal subscription