Glucokinase Activators

Glucokinase is an enzyme involved in the control of energy balance that plays a key role in glycolytic flux control. By phosphorylating glucose in multiple key organs, such as liver, pancreas, intestine and brain, GK acts as a glucose sensor, controlling both glucose induced insulin secretion in beta cells and glucose metabolism in the liver.

The role of GK in glucose metabolism have been emphasized by loss-of-function mutations in the gene coding for GK, linked to maturity onset diabetes of the youth type 2 (MODY 2 characterized by impaired glucose responsiveness of beta cells, decreased glycogen accumulation and increased hepatic glucose production after meals) and by gain-of-function mutations linked to persistent hyperinsulinemic hypoglycemia of infancy as a result of lowering the threshold for glucose stimulated insulin release (GSIR).

Glucokinase activators (GKA) will restore appropriated glucose sensing, i.e. insulin secretion in response to glucose, hepatic glucose output and GLP1 secretion.

Glucokinase Activators Mechanism of Action

The project is currently at the lead discovery stage at Poxel.