DEVELOPMENT OF DECREASED INSULIN-INDUCED GLUCOSE-TRANSPORT IN SKELETAL-MUSCLE OF GLUCOSE-INTOLERANT HYBRIDS OF DIABETIC GK RATS

1. The effect of glucose intolerance on insulin-stimulated glucose transport in isolated skeletal muscles was investigated in male F-1 hybrids of spontaneously diabetic GK (Goto-Kakizaki) and control Wistar rats at 1 and 2 months of age. 2. Hybrid rats are characterized by markedly impaired glucose-induced insulin secretion. The area under the blood glucose curve was significantly higher following an intraperitoneal glucose injection (2 g/kg) in hybrid rats in both age groups than in the control rats (P < 0.001). In 2-month-old hybrid rats the incremental area under the insulin curve during the intraperitoneal glucose tolerance test was not different from that of control rats. Serum cholesterol, triacylglycerol or plasma free fatty acid levels did not differ between the groups. Fasting and post-prandial plasma glucose concentrations were elevated in 2-month-old hybrid rats compared with control rats (54%, P < 0.05, and 27%, P < 0.05, respectively), but were not different in 1-month-old rats. Plasma insulin did not differ between the hybrid and control rats in the fasting or post-prandial state at either age studied. 3. The insulin dose-response curves for 3-O-methylglucose transport did not differ between 1-month-old hybrid and control rats for either the soleus or epitrochlearis muscle. The insulin dose-response curve for the epitrochlearis, but not for the soleus, muscle from 2-month-old hybrid rats was shifted to the right compared with the curve from the control animals (P < 0.05). 4. In conclusion, the hybrid rat is a non-obese, non-hyperinsulinaemic animal model, which at a young age is characterized by impaired insulin secretion and moderate glucose intolerance. In this glucose-intolerant rat model, mild peripheral insulin resistance gradually develops, as reflected by the decreased insulin-induced glucose transport in the fast-twitch epitrochlearis muscle. It is suggested that the elevated blood glucose per se may have contributed to the slight decrease in peripheral insulin action.