Recent advances in glucokinase activators for the treatment of type 2 diabetes

Glucokinase is a member of the hexokinase family of enzymes that are responsible for the phosphorylation of glucose to glucose-6-phosphate for further utilization in cells. The enzyme plays a key role in glucose homeostasis. Phosphorylation of glucose by glucokinase in the liver promotes glycogen synthesis, while in the β-cell it results in insulin release. Activators of glucokinase increase the sensitivity of the enzyme to glucose, leading to increased insulin secretion and liver glycogen synthesis and a decrease in liver glucose output. Thus, small molecule glucokinase activators have been demonstrated to be effective glucose-lowering agents in animal models of type 2 diabetes and have advanced into clinical studies.