Glucokinase Inhibition: A Novel Treatment for Diabetes?

Chronic hyperglycemia increases pancreatic b-cell metabolic activity, contributing to glucotoxicity-induced b-cell failure and loss of functional b-cell mass, potentially in multiple forms of diabetes. In this perspective we discuss the novel paradoxical and counterintuitive concept of inhibiting glycolysis, particularly by targeted inhibition of glu-cokinase, the first enzyme in glycolysis, as an approach to maintaining glucose sensing and preserving functional b-cell mass, thereby improving insulin secretion, in the treatment of diabetes.