Tetsuo Kaneko

Effect of 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 microM) dose-dependently 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 cAMP-dependent protein kinase (PKA) inhibitor inhibited hepatic gluconeogenesis, the drug did not intensify the inhibitory effect of CRA on hepatic gluconeogenesis in isolated hepatocytes. These results indicate that CRA inhibits gluconeogenesis by increasing the production 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.

Enhancing Effect of Dietary Oil Emulsions on Immune Responses to Protein Antigens Fed to Mice

Repeated intragastric administration of β-lactoglobulin (β-Lg) with emulsified soybean oil elicited an antigen-specific, systemic humoral immune response in different strains of mice. The antibody response was enhanced as the dose of oil was increased and the particle size of emulsions was decreased. Feeding of aqueous β-Lg could induce the antibody response only when emulsified oil was fed almost simultaneously. However, the emulsion-driven humoral immune response was not observed when mice were treated with anti-CD40 ligand antibody or in athymic mice. It is likely that the intestinal coexistence of emulsified oil with dietary antigens modulates the immune system to crucially support B cell response. A practical application of the present results to the prevention of cow’s milk protein sensitization in infants is proposed.