Insulin action in growth hormone-deficient and age-matched control rats: effect of growth hormone treatment

The isolated effect of growth hormone on carbohydrate metabolism in rat skeletal muscle was studied in growth hormone-deficient dwarf rats (dw/dw) treated with either recombinant human growth hormone or saline for 10 days. In addition, age-matched heterozygous (DW/dw) (normal weight and plasma IGF-I) control rats were treated with saline. Growth hormone increased weight gain from 0.1+/-0.1 (s.e.m) to 3.6+/-0.1 g/day and plasma IGF-I concentration from 364+/-23 to 451+/-32 ng/ml. Glucose metabolism in skeletal muscle perfused with basal, submaximal and maximal concentrations (0, 600 and 60 000 pmol/l respectively) of insulin was not changed by growth hormone. No change could be detected in the total number of glucose transporters (GLUT1 and GLUT4) in the skeletal muscles, except from a lower amount of GLUT4 in the soleus muscle in the heterozygous control group. However, at submaximal insulin concentrations, skeletal muscle glucose uptake and transport were significantly lower in the heterozygous control group compared with the growth hormone-deficient group. This could indicate either a direct long-term effect of growth hormone or more likely a secondary effect attributable to the difference in body weight (205.2+/-3.1 vs 361. 6+/-5.9 g for dwarf rats and heterozygous controls respectively), and thereby muscle fibre size, between the groups probably resulting in lower average interstitial insulin and glucose concentrations at a given plasma concentration in the heterozygous rats. It is concluded that restoration of subnormal growth hormone concentrations for 10 days has no effect on insulin-stimulated glucose metabolism in skeletal muscle in vitro.