Insulin resistance and impaired glucose tolerance in the atherosclerosis-prone LA/N corpulent rat

The LA/N-cp rat is, when homozygous for the cp gene, hyperphagous, hyperlipidemic, and corpulent. The corpulent males develop atherosclerotic disease and myocardial lesions while corpulent females and lean rats do not. The fasting plasma glucose concentrations of corpulent rats are in the normal range, but insulin concentrations are mildly elevated in corpulent females and markedly elevated in corpulent males. Glucose tolerance testing reveals a glucose intolerance in corpulent rats in the presence of very high insulin concentrations, and this deficiency is more severe in the male rats. Glucagon concentrations are higher in corpulent rats than lean rats at 3 months of age and decrease progressively with age. In contrast, glucagon concentrations increase with age in lean rats and are higher than those in corpulent rats at 9 months. The islets of Langerhans of corpulent rats exhibit marked hyperplasia that increases with age. The hyperplasia is less extreme in corpulent female rats. The abnormalities suggest that this strain of rats has an insulin resistance leading to impaired glucose tolerance and progressive pancreatic disturbance. This process may be related to an accompanying defect causing elevated concentrations of very low density lipoproteins and correlates with the development of atherosclerotic disease.