咖啡酸及肉桂酸減輕小鼠肝臟細胞 (FL83B) 胰島素阻抗及改善碳水化合物代謝之研究

Abstract

Diabetes mellitus (DM) is a chronic disease associated with carbohydrate metabolism and caused by a deficiency in insulin secretion or by the ineffectiveness in insulin action. About 95% of the diabetic incidences belong to type 2 diabetes, of which the main cause of hyperglycemia is the ineffectiveness in insulin action or the inability to induce a normal response to insulin in the cells. Two phenolic acids, caffeic acid and cinnamic acid, are commonly present in fruits, vegetables, and coffee. Anti-hyperglycemic activity has become a focus in recent studies on these two phenolic acids. The present study investigated the effect of the two phenolics on enhancing glucose uptake and ameliorating carbohydrate metabolism in TNF-α-induced insulin resistant mouse liver FL83B cells.The uptake test of 2-[1-14C ] deoxy-D-glucose in insulin resistant FL83B cells was performed to evaluate the hypoglycemic effect. The expressions of insulin signal proteins, glycogen synthesis associated enzymes and the enzymes of gluconeogenesis were analyzed to elucidate the enhancement on glucose uptake and the restoration on glycogen synthesis in insulin resistant FL83B cells by the phenolic acids.. In the results of antihyperglycemic effect, the two phenolic acids promote insulin receptor tyrosyl phosphorylation, up-regulat the expression of insulin signal associated proteins, including insulin receptor, phosphatidylinositol-3 kinase (PI3K), glycogen synthase (GS), and glucose transporter-2 (GLUT-2). The results of amelioration on carbohydrate metabolism revealed that the two phenolic acids increase the expression of Glucokinase (GK), while decrease the expression of glycogen synthase kinase (GSK), Ser-641 phosphorylation of GS, hepatic nuclear factor-4 (HNF-4), and phosphoenolpyruvate carbooxykinase (PEPCK) in the resistant cells. In conclusion, we speculate that caffeic acid and cinnamic acid may improve glucose uptake and ameliorate carbohydrate metabolism by restoring isulin sensitivity in insulin resistant FL83B cells. These two phenolic acids may restore glycogen synthesis, promote glucose uptake into cells, inhibit gluconeogehesis to decrease glucose formation, and result in the alleviation of insulin resistance in cells as the consequence.