Wang Xiao, Zhou Libin, Shao Li, Qian Lei, Fu Xuelian, Li Guo, Luo Tianhong, Gu Yanyun, Li Fengying, Li Jiping, Zheng Sheng, Luo Min
Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Life Sci. 2007 Jun 20;81(2):160-5. doi: 10.1016/j.lfs.2007.04.034. Epub 2007 May 6.
Changes in AMP-activated protein kinase (AMPK) activity contribute to the regulation of insulin secretion. Troglitazone has been shown to lower serum insulin levels and protect beta cell function. The aim of the present study was to examine the effects of troglitazone on AMPK activity and insulin secretion in beta cells. Isolated rat islets and MIN6 cells were treated for a short (1 h) or a long time (20 h) with troglitazone. One-hour troglitazone treatment activated AMPK and inhibited both glucose-stimulated insulin secretion (GSIS) and the response of insulin secretion to combined stimuli of glucose and palmitate. Long (20 h) treatment with troglitazone caused a sustained phosphorylation of AMPK and acetyl-CoA carboxylase, and increased GSIS after withdrawal of the drug. This study provided evidence that troglitazone activated AMPK in beta cells. In addition to the insulin-sensitizing effects in peripheral tissues, troglitazone also directly inhibits insulin hypersecretion by the elevated glucose and fatty acids, and thus protects beta cells from glucolipotoxicity.
AMP激活的蛋白激酶（AMPK）活性的变化有助于胰岛素分泌的调节。已证明曲格列酮可降低血清胰岛素水平并保护β细胞功能。本研究的目的是研究曲格列酮对β细胞中AMPK活性和胰岛素分泌的影响。将分离的大鼠胰岛和MIN6细胞用曲格列酮短时间（1小时）或长时间（20小时）处理。曲格列酮处理1小时可激活AMPK，并抑制葡萄糖刺激的胰岛素分泌（GSIS）以及胰岛素分泌对葡萄糖和棕榈酸联合刺激的反应。曲格列酮长时间（20小时）处理导致AMPK和乙酰辅酶A羧化酶的持续磷酸化，并在停药后增加GSIS。本研究提供了曲格列酮在β细胞中激活AMPK的证据。除了在外周组织中的胰岛素增敏作用外，曲格列酮还通过升高的葡萄糖和脂肪酸直接抑制胰岛素过度分泌，从而保护β细胞免受糖脂毒性。
