Effects of advancing age and severe food restriction on pathological processes in the insulin resistant JCR:LA-corpulent rat.

Corpulent rats of the JCR:LA-corpulent strain spontaneously develop atherosclerotic lesions, occlusive thrombi and myocardial lesions. In addition to exhibiting a VLDL hyperlipidemia they are insulin resistant. Young male corpulent rats have significantly impaired rates of clearance of plasma glucose on an intravenous glucose tolerance test in comparison to lean rats (k = 0.94 +/- 0.69 vs 2.06 +/- 0.64 x 10(-2) min-1, p less than 0.01). Food restriction to 60% of the spontaneous intake of lean controls (12 g/day) for 10 days raised the rate of glucose clearance to that of the lean rats (k = 3.01 +/- 0.40 x 10(-2) min-1) and this was highly significant compared to the rate at three months of age (p less than 0.0005). Food restriction significantly lowered the elevated insulin levels of corpulent rats at 3 and 12 months of age. It inhibited, but did not prevent, the development of hyperplasia of the islets of Langerhans. The hypertriglyceridemia was less severe in 12 month old rats (214 +/- 52 vs 282 +/- 19 mg/100 ml while total cholesterol was increased (129 +/- 20 vs 85 +/- 5.5 mg/100 ml). Severe food restriction halved the triglyceride concentration at both 3 and 12 months of age while total cholesterol was unaffected. The food restriction throughout life up to 12 months of age, however, did inhibit the development of advanced myocardial lesions.