The role of glucose and its metabolism in the regulation of glucokinase expression in isolated human pancreatic islets

Previous reports concerning the regulation of glucokinase expression in bet a cells have been done using cell models from rodent origin. Evidence is la cking so far to implicate the same regulatory mechanisms in human cells. In this study, we investigate the effects of glucose on the expression of glu cokinase using isolated human pancreatic islets. High glucose (16.7 mM), in a time-dependent manner, increases the amount of immunoreactive glucokinas e (+150% after 7 days culture, P < 0.01) without apparent changes in glucok inase gene expression, suggesting that glucose exerts its effect at a postt ranscriptional level. Mannose, but not the nonmetabolized hexoses, 3-O-meth ylglucose or a-deoxyglucose, increases glucokinase protein content. Even th ough these findings are compatible with an involvement of signals derived f rom glucose metabolism, additional data argue against this hypothesis: (i) a glucokinase inhibitor (mannoheptulose) does not block glucose-induced inc rease in glucokinase content and (ii) other metabolic fuels (amino acids) a re ineffective. We suggest that the glucose molecule, by mechanisms yet to be defined, but probably not involving its metabolism, regulates human gluc okinase expression. (C) 2000 Academic Press.