Overexpression Of Human Insulinoma Pfk2/F2,6dpase In Rat Primary Cultured Hepatocytes - A Key Role Of F2,6dp In Glucagon Effects On Hepatic Glucose Metabolism

To elucidate the role of F2.6DP in hepatic glucose metabolism, especially in the regulatory mechanism of glucagon, wild type (WT) and mutant type (193A:PFK2 activity is abolished) human insulinoma PFK2/F2,6DPase was expressed in rat primary cultured hepatocytes via a recombinant adenovirus vector. The beta GaL gene was transferred into control cells (CONT). Glucagon markedly decreased F2,6DP contents and suppressed both oxidation and utilization of glucose in CONT. while glucagon did not affect F2,6DP contents, glucose oxidation, or glucose utilization in WT. The F2,6DP content was significantly decreased in 193A as compared with CONT and WT, and glucose utilization in 193A was significantly decreased as compared with CONT. These results demonstrate that F2,6DP is a crucial component of hepatic glucose metabolism. Accordingly, it is possible that gene defects in PFK2/F2,6DPase are responsible for some forms of abnormal glucose homeostasis in humans.