Carbon Dioxide: A Pre-Requisite for Increased Hepatic Glucose Production in Type 2 Diabetes

Type 2 diabetic patient have an increased rate of production of hepatic glucose which leads to persistent hyperglycemia. The increase in hepatic glucose production was found to be due to availability and uptake of gluconeogenic substrates, but that alone cannot drive glucose synthesis. Carbon dioxide produced at the end of metabolic combustion of fuel is then used as a substrate for the first step in hepatic glucose production i.e the pyruvate carboxylase reaction. Decrease in carbon dioxide is associated with decrease in hepatic glucose production. Furthermore, inhibition of carbonic anhydrase which interconverts carbon dioxide and bicarbonate has been found to decrease hepatic glucose synthesis. Therefore, it can be concluded that increased substrate delivery to the liver and increased efficiency of hepatic substrate uptake alone cannot drive glucose synthesis that continues supply of carbon dioxide is necessary for hepatic glucose production.