Perspectives in Diabetes Hexosamines and Insulin Resistance

Glucose is an important regulator of cell growth and metabolism. Thus, it is likely that s m e of the adverse effects of hyperglycemia are reflections of normal regulation by abnormal concentrations of glacose. How the cell senses glucose, however, is still incom~letely understood. Evidence has been presented that the hexosamine biosynthesis pathway serves this function for regulation of aspects of glucose uptake, glycogen synthesis, glycolysis, and synthesis of growth factors. Excess hexosamine flux causes insulin resistance in cultured cells, tissues, and intact animals. Further evidence for the possible role of this pathway in normal glucose homeostasis and disease is that the level of activity of the rate-biting enzyme in hexosamine synthesis, glutamine:fructose-6-phosphate amidotransferase, is correlated with glucose disposal rates (GDRs) in normal humans and transgenic mice. Diabetes 45:1003-1009,1996