Jung Un Ju, Lee Mi-Kyung, Park Yong Bok, Jeon Seon-Min, Choi Myung-Sook
Institute of Genetic Engineering, Kyungpook National University, Daegu, Korea.
J Pharmacol Exp Ther. 2006 Aug;318(2):476-83. doi: 10.1124/jpet.106.105163. Epub 2006 Apr 27.
This study investigated the blood glucose-lowering effect and antioxidant capacity of caffeic acid in C57BL/KsJ-db/db mice. Caffeic acid induced a significant reduction of the blood glucose and glycosylated hemoglobin levels than the control group. The plasma insulin, C-peptide, and leptin levels in caffeic acid group were significantly higher than those of the control group, whereas the plasma glucagon level was lower. Increased plasma insulin by caffeic acid was attributable to an antidegenerative effect on the islets. Caffeic acid also markedly increased glucokinase activity and its mRNA expression and glycogen content and simultaneously lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities and their respective mRNA expressions, accompanied by a reduction in the glucose transporter 2 expression in the liver. In contrast to the hepatic glucose transporter 2, adipocyte glucose transporter 4 expression was greater than the control group. In addition, caffeic acid significantly increased superoxide dismutase, catalase, and glutathione peroxidase activities and their respective mRNA levels, while lowering the hydrogen peroxide and thiobarbituric acid reactive substances levels in the erythrocyte and liver of db/db mice. These results indicate that caffeic acid exhibits a significant potential as an antidiabetic agent by suppressing a progression of type 2 diabetic states that is suggested by an attenuation of hepatic glucose output and enhancement of adipocyte glucose uptake, insulin secretion, and antioxidant capacity.
本研究调查了咖啡酸对C57BL/KsJ-db/db小鼠的降血糖作用及抗氧化能力。与对照组相比，咖啡酸显著降低了血糖和糖化血红蛋白水平。咖啡酸组的血浆胰岛素、C肽和瘦素水平显著高于对照组，而血浆胰高血糖素水平较低。咖啡酸使血浆胰岛素增加归因于对胰岛的抗退变作用。咖啡酸还显著增加了葡萄糖激酶活性及其mRNA表达以及糖原含量，同时降低了葡萄糖-6-磷酸酶和磷酸烯醇丙酮酸羧激酶活性及其各自的mRNA表达，伴有肝脏中葡萄糖转运蛋白2表达减少。与肝脏葡萄糖转运蛋白2相反，脂肪细胞葡萄糖转运蛋白4表达高于对照组。此外，咖啡酸显著增加了超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性及其各自的mRNA水平，同时降低了db/db小鼠红细胞和肝脏中的过氧化氢和硫代巴比妥酸反应性物质水平。这些结果表明，咖啡酸通过抑制2型糖尿病状态的进展（表现为肝脏葡萄糖输出减少、脂肪细胞葡萄糖摄取增加、胰岛素分泌增加和抗氧化能力增强），展现出作为抗糖尿病药物的显著潜力。
