Mutations of the human glucokinase gene and diabetes mellitus.

Abstract The enzyme glucokinase catalyzes the phosphorylation of glucose and plays a key role in the regulation o f insulin secretion by pancreatic β cells and glucose disposal in hepatocytes. Recent studies have shown that mutations in the gene encoding this key regulatory enzyme of glycolysis are a common cause of an autosomal dominant form of non-insulin-dependent (type 2) diabetes mellitus that has an onset often during childhood. The association of mutations in the glucokinase gene with impaired pancreatic cell function underscores the importance of glycolysis in the regulation of insulin secretion and suggests that mutations in other genes expressed in the β-cell that also control rate-limiting steps in glucose metabolism may lead to diabetes.