Insulin resistant glucose transport activity in adipose cells from the SHR/N-corpulent rat

Young male obese (cp/cp) and lean (cp/+ or +/+) littermates of the SHR/N-corpulent (cp) strain were fed purified diets containing 54% carbohydrate as either sucrose or cooked starch for 12 wk. A significant effect of phenotype (obese greater than lean) was observed on body weight, epididymal fat pad weight and fat cell size. A diet effect (sucrose greater than starch) was observed on body weight, fat pad weight, and fat cell size. No effect of phenotype or diet was observed on basal 3-O-methylglucose transport in isolated adipose cells. However, insulin-stimulated glucose uptake was decreased 70-80% in isolated adipose cells from obese SHR/N-cp rats. No effect of diet on insulin-stimulated glucose uptake was observed in obese SHR/N-cp rats. Scatchard analysis of insulin binding data demonstrated no differences in the dissociation constant (KD) for the insulin receptor:insulin complex. However, obese rats exhibited a decreased number of insulin receptors compared to lean SHR/N-cp rats. These data demonstrate that the obese SHR/N-cp rat exhibits insulin-resistant glucose transport. This altered insulin sensitivity may be one factor contributing to the development of noninsulin-dependent diabetes mellitus in these animals.