GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE ACTIVITY IN CULTURED HUMAN SKELETAL-MUSCLE CELLS - RELATIONSHIP TO GLUCOSE DISPOSAL RATE INCONTROL AND NON-INSULIN-DEPENDENT DIABETES-MELLITUS SUBJECTS AND REGULATION BY GLUCOSE AND INSULIN

We examined the activity of the rate-limiting enzyme for hexosamine bi osynthesis, glutamine:fructose-6-phosphate amidotransferase (GFA) in h uman skeletal muscle cultures (HSMC), from 17 nondiabetic control and 13 subjects with non-insulin-dependent diabetes. GFA activity was assa yed from HSMC treated with low (5 mM) or high (20 mM) glucose and low (22 pM) or high (30 mu M) concentrations of insulin. In control subjec ts GFA activity decreased with increasing glucose disposal rate (r = - 0.68, P < 0.025). In contrast, a positive correlation existed between GFA and glucose disposal in the diabetics (r = 0.86, P < 0.005), Incre ased GFA activity was also correlated with body mass index in controls but not diabetics. GFA activity was significantly stimulated by high glucose (22%), high insulin (43%), and their combination (61%). GFA ac tivity and its regulation by glucose and insulin were not significantl y different in diabetic HSMC. We conclude that glucose and insulin reg ulate GFA activity in skeletal muscle. More importantly our results ar e consistent with a regulatory role for the hexosamine pathway in huma n glucose homeostasis. This relationship between hexosamine biosynthes is and the regulation of glucose metabolism is altered in non-insulin- dependent diabetes.