Lack of deterioration of insulin action with aging in the GK rat: A contrasted adaptation as compared with nondiabetic rats

One of the main characteristics of non-insulin-dependent diabetes mellitus (NIDDM) is an alteration of tissue insulin sensitivity, which is also observed during the aging process in the nondiabetic. In this study, we evaluated the influence of age on insulin resistance in a genetic lean model of NIDDM, the Goto-Kakisaki (GK) rat, using the euglycemic-hyperinsulinemic clamp technique at 2, 12, and 18 months of age. In GK rats, basal hyperglycemia (11 nmol/L) and insulinemia, glucose intolerance, and the specific failure of the insulin response to glucose apparent at 2 months of age remained stable until 18 months. Whatever the age, the insulin-suppressive effect on glucose production was significantly less in GK rats than in Wistar rats. The insulin effect on whole-body glucose utilization was decreased at 2 months (15.8 +/- 1.0 mg/min/kg v 23.5 +/- 2.0, P < .001) and was only mildly aggravated between 2 and 18 months (10.3 +/- 0.9 mg/min/kg, P < .05). By contrast, in Wistar control rats, basal insulinemia and the insulin response to glucose markedly increased between 2 and 18 months (2-month Delta I v 18-month Delta I, 1.4 +/- 0.1 mU/ml . min v 2.9 +/- 0.3, P < .001) and glucose tolerance remained normal. In 18-month-old Wistar rats, the insulin-stimulated glucose utilization rate (GUR) was found to be markedly decreased compared with that of 2-month-old Wistar rats (9.9 +/- 0.8 mg/min/kg v 23.5 +/- 2.0, P < .001), thus demonstrating an age-related decrease of insulin action. In conclusion, we find that there is no major alteration of insulin action due to aging in the GK rat, at variance with the pattern in nondiabetic rodents. It is speculated that such an adaptation in this lean model of NIDDM could be related to the limited capacity of these rats to expand their body weight with age, since it is recognized that body weight gain is largely responsible for the age-related impairment in peripheral insulin action in nondiabetic humans and nondiabetic animal models. Copyright (C) 1997 by W.B. Saunders Company.