The Role of Carbonic Anhydrase in Hepatic Glucose Production

Background: Carbonic anhydrase is a ubiquitous zinc metalloenzyme in organisms that primarily catalyzes the reversible hydration of CO2 to HCO3 - and H+. It is involved in many important physiological and pathological conditions such as electrolyte secretion and biosynthetic reaction like gluconeogenesis, lipogenesis and ureagenesis. The enzyme provides HCO3 - as a substrate for pyruvate carboxylase, the first enzyme in hepatic gluconeogenesis. The present review showed that carbonic anhydrase is the main driver of hepatic gluconeogenesis. Methods: Google scholar and Medline Embase (inception to 2015) were searched for studies on mechanism of hepatic glucose production, increased hepatic glucose production in diabetes and changes in carbonic anhydrase activity in diabetes and its treatment. Results: Many studies have linked changes in carbonic anhydrase activity with the development and progression of diabetes mellitus. Carbonic anhydrase has been shown to provide HCO3 - as substrate for the first reaction of hepatic gluconeogenesis which has also been reported to increase significantly in type 2 diabetes. Increase in carbonic anhydrase activity increases the availability of these substrates and in turn increases hepatic glucose production. Conclusion: Carbonic anhydrase can be said to be the key factor responsible for reduction of hepatic glucose production. Thus carbonic anhydrase could serve as a new therapeutic target for reducing hepatic glucose production.