[Insulin resistance: lessons from animal models of obesity]

The insulin resistance of animal models of obesity (the gold thioglucose obese mouse and the o b/o b mouse) is characterized by several abnormalities. At the receptor step, both the binding function (decreased number of sites) and the enzymatic, tyrosine kinase function (decreased insulin activation) are altered. At postreceptor steps, phosphatidylinositol 3-kinase (PI3-K) plays an important role in insulin signalling, particularly for the stimulation of glucose transport in muscle and adipocyte. Insulin activation of PI3-K is markedly diminished in obese mice; starving the obese animals restores normal responses of PI3-K, glucose transport, and glycogen synthesis, to insulin. These observations emphasize the multi-site, and largely reversible, nature of insulin resistance in these animal models of obesity. Similar alterations have been reported in the literature with regard to the sites of insulin resistance in human obesity and non insulin-dependent diabetes.