Carbonic Anhydrase: A New Therapeutic Target for Managing Diabetes

Abstract

Background: Carbonic Anhydrase (CA) is a zinc metallo-enzyme that is critical to regulation of systemic acid-base homeostasis by facilitating urinary acidification. Inhibition of carbonic anhydrase results in metabolic acidosis which leads to decrease in pH. Aim and objectives: The study aims to highlight the potential utility of erythrocyte carbonic anhydrase as therapeutic target for managing diabetes, by investigating changes of erythrocyte carbonic anhydrase activity in STZ induced diabetic rats. Methods: Carbonic anhydrase activity was determined by the absorbance of p-nitrophenol at 345nm released from p-nitrophenyl acetate. HbA1c was determined by ion exchange method (Spectrum diagnostics). Biochemical parameters were determined by Accutrend GCT meters with cobias® test strips. Results: The result revealed that inhibition of erythrocyte carbonic anhydrase results in significant increase in both blood lactate concentration and HbA1c level with significant reduction in blood glucose concentration. Metformin was found to reduce carbonic anhydrase activity and HbA1c level significantly and increased blood lactate concentration. The extract of Cadaba farinosa was found to reduce blood glucose concentration. Conclusions: Inhibition of carbonic anhydrase can be associated with reduced circulating blood glucose level. Metformin may therefore reduce circulating blood glucose by inhibiting carbonic anhydrase. Increased level of HbA1c may probably be due to inhibition of erythrocyte carbonic anhydrase. Therefore Carbonic anhydrase can potentially serve as a therapeutic target for managing diabetes in combination as serving as valuable marker for lactic acidosis.