La. Nolte et al., DEVELOPMENT OF DECREASED INSULIN-INDUCED GLUCOSE-TRANSPORT IN SKELETAL-MUSCLE OF GLUCOSE-INTOLERANT HYBRIDS OF DIABETIC GK RATS, Clinical science, 88(3), 1995, pp. 301-306
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.