Glucokinase activators: molecular tools for studying the physiology of insulin-secreting cells.

GK (glucokinase) catalyses the phosphorylation of glucose to glucose 6-phosphate in glucosensitive cells. In pancreatic beta-cells, this reaction is the rate-limiting step of insulin release. Recent work has led to the discovery of synthetic small-molecule activators of GK that stimulate beta-cell physiology and subsequently enhance the glucose-dependent release of insulin. It is currently recognized that these compounds may represent a significant advance in the development of new agents in the treatment of diabetes. In addition, GKAs (GK activators) are emerging as reagents that are useful tools with which to probe the function of pancreatic beta-cells and other glucosensitive cells. This includes providing insights into the physiology of the beta-cell by helping to elucidate the kinetic cycle of GK, confirming the central role of glucose metabolism to the beta-cell and highlighting subtle species-dependent differences in insulin secretion between rodent and human islets of Langerhans.