In vivo hepatic and peripheral insulin sensitivity in rats with non-insulin-dependent diabetes induced by streptozocin. Assessment with the insulin-glucose clamp technique.

Non-insulin-dependent diabetes mellitus (NIDDM) was obtained in adult female rats by neonatal administration of streptozocin (STZ). At 2 mo of age, the basal plasma glucose values in the postabsorptive state were elevated, the glucose disappearance rate measured after intravenous (i.v.) glucose load was significantly lower in the diabetic than in control rats, and in vivo glucose-induced insulin release was drastically reduced. To quantify and characterize the in vivo insulin sensitivity in rats with NIDDM, we have used the insulin-glucose clamp technique. The effects of different concentrations of insulin on glucose production, glucose utilization, and glucose clearance (measured by using 3-3H-glucose) were studied in anesthetized diabetic or control rats while in the postabsorptive state. An inherent condition to set up a valid experimental design was to take into consideration, in the diabetics, the influence of the high blood glucose concentration on glucose uptake and glucose production, since the blood glucose concentration by itself affects these two parameters by a mass action effect independent of insulin. The issue was addressed by evaluating glucose production and utilization in three experimental groups: diabetics clamped at their basal blood glucose level (170 mg/dl), controls clamped at their basal blood glucose level (110 mg/dl), and controls clamped at high blood glucose level (170 mg/dl). In the basal state, glucose production was significantly higher in the diabetics than in controls. When plasma insulin was clamped at submaximal levels (300 microU/ml), the suppression of glucose production was significantly more important in the diabetics than in the two control groups.(ABSTRACT TRUNCATED AT 250 WORDS)