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 tra nsport in isolated skeletal muscles was investigated in male F-1 hybri ds of spontaneously diabetic GK (Goto-Kakizaki) and control Wistar rat s at 1 and 2 months of age. 2. Hybrid rats are characterized by marked ly impaired glucose-induced insulin secretion. The area under the bloo d glucose curve was significantly higher following an intraperitoneal glucose injection (2 g/kg) in hybrid rats in both age groups than in t he control rats (P < 0.001). In 2-month-old hybrid rats the incrementa l area under the insulin curve during the intraperitoneal glucose tole rance test was not different from that of control rats. Serum choleste rol, triacylglycerol or plasma free fatty acid levels did not differ b etween the groups. Fasting and post-prandial plasma glucose concentrat ions were elevated in 2-month-old hybrid rats compared with control ra ts (54%, P < 0.05, and 27%, P < 0.05, respectively), but were not diff erent in 1-month-old rats. Plasma insulin did not differ between the h ybrid and control rats in the fasting or post-prandial state at either age studied. 3. The insulin dose-response curves for 3-O-methylglucos e transport did not differ between 1-month-old hybrid and control rats for either the soleus or epitrochlearis muscle. The insulin dose-resp onse curve for the epitrochlearis, but not for the soleus, muscle from 2-month-old hybrid rats was shifted to the right compared with the cu rve from the control animals (P < 0.05). 4. In conclusion, the hybrid rat is a non-obese, non-hyperinsulinaemic animal model, which at a you ng age is characterized by impaired insulin secretion and moderate glu cose intolerance. In this glucose-intolerant rat model, mild periphera l insulin resistance gradually develops, as reflected by the decreased insulin-induced glucose transport in the fast-twitch epitrochlearis m uscle. It is suggested that the elevated blood glucose per se may have contributed to the slight decrease in peripheral insulin action.