CLARIFICATION OF THE MECHANISM OF ANIT-DIABETIC EFFET BY THE ADMINISTRATION OF BIOTIN

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Biotin is one of water-soluble vitamin that functions as a cofactor of four types of carboxylase involved in lipid, carbohydrate and amino acids metabolism in mammalian. Our group has shown that biotin has a novel function that improves carbohydrate metabolism in diabetes mellitus. This research aimed clarification of mechanism of this novel action of biotin.First of all, we tried to identify site to action of biotin in the stimulation of insulin secretion from the B cells of pancreas. The Langerhan's islet was isolated from rat pancreas, and cultured. Secreted insulin in cultured medium was measured after stimulation of glucose with or without biotin. The secretion of insulin has been increased by biotin administration dose-dependent manner (up to 50μM). This phenomenon was observed when pyruvate was used as a stimulant instead of glucose, therefore biotin was presumed to be participation in the reaction within mitochondria on the glycolytic pathway. Then, the ability of oxidative pho … More sphorylation at the TCA cycle was measured by using radioisotope of glucose with a different labeling site. As a result, the amount of ^<14>CO_2 formations was increased twice by biotin administration when [U-^<14>C] glucose was used as a stimulant, while it was not changed in case of [6-^<14>C] glucose administration. These results indicate that biotin could stimulate ATP synthesis through significant increase of glucose oxidation without the change of rotation ability in TCA cycle.Next, we analyzed the involvement of biotin in the regulation of liver phosphoenolpyruvate carboxykinase (PEPCK) gene expression. PEPCK mRNA was decreased by 40% compared with the control when the biotin was administered to the streptozotocin induced diabetic rat. Therefore biotin has insulin-like action and could improve the condition of diabetic animal. We tried to identify the site of biotin regulation of PEPCK gene using rat hepatoma cell H4IIE that has the insulin susceptibility. PEPCK mRNA increased in H4IIE cells 3 hours after treatment of biotin when cells were incubated with insulin medium. This result indicated that biotin could suppress the insulin action in this cell line. Less