Familial adult onset hyperinsulinism due to an activating glucokinase mutation: implications for pharmacological glucokinase activation

摘要

ContextGlucokinase (GCK) phosphorylates and thereby traps glucose in cells, thus serving as a gatekeeper for cellular glucose metabolism, particularly in hepatocytes and pancreatic beta cells. In humans, activating GCK mutations cause familial hyperinsulinaemic hypoglycaemia (GCK-HH), leading to keen interest in the potential of small-molecule glucokinase activators (GKAs) as treatments for diabetes mellitus. Many such agents have been developed; however, observation of side effects including hypertriglyceridaemia and hepatic steatosis has delayed their clinical development.