corosolic acid on gluconeogenesis in rat liver

Corosolic acid (CRA), an active component of Banaba leaves (Lagerstroemia speciosa L.), decreases blood glucose in diabetic animals and humans. In this study, we investigated the mechanism of action of CRA on gluconeogenesis in rat liver. CRA (20–100 mM) dosedependently decreased gluconeogenesis in perfused liver and in isolated hepatocytes. Fructose-2,6-bisphosphate (F-2,6-BP), a gluconeogenic intermediate, plays a critical role in hepatic glucose output by regulating gluconeogenesis and glycolysis in the liver. CRA increased the production of F-2,6-BP along with a decrease in intracellular levels of cAMP both in the presence and in the absence of forskolin in isolated hepatocytes. While a cAMPdependent protein kinase (PKA) inhibitor inhibited hepatic gluconeogenesis, the drug did not intensify the inhibitory effect of CRA on hepatic gluconeogenesis in isolated hepatocytes.These resultsindicatethatCRA inhibits gluconeogenesis byincreasing theproduction of F-2,6-BP by lowering the cAMP level and inhibiting PKA activity in isolated hepatocytes. Furthermore, CRA increased glucokinase activity in isolated hepatocytes without affecting glucose-6-phosphatase activity, suggesting the promotion of glycolysis. These effects on hepatic glucose metabolism may underlie the various anti-diabetic actions of CRA.

Banaba leaves (Lagerstroemia speciosa L.) have been used as a popular traditional medicine in Southeast Asia, and tea made from the leaves has been used to treat diabetes mellitus. The leaves contain large amounts of corosolic acid (CRA),which has recently attracted much attention due to its effects of CRA on liver are not well known. The liver is a key regulatory organ of glucose homeostasis, taking up glucose in the fed state and releasing glucose into circulation during starvation, exercise, and when the ratio of insulin to counterinsulin factors is decreased, maintaining blood glucose levels within a narrow physiological range. Impairments in hepatic glucoseuptakeandproductionbotharecharacteristicfeatures of the diabetic state.

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