Park Sunmin, Hong Sang Mee, Sung So Ra
Department of Food & Nutrition, College of Natural Science, Hoseo University, Asan-Si, South Korea.
Life Sci. 2008 Feb 27;82(9-10):503-11. doi: 10.1016/j.lfs.2007.12.018. Epub 2007 Dec 31.
Not only exendin-4 but also exercise has been reported to improve glucose homeostasis by enhancing insulinotropic action, but the nature of its molecular mechanism has not been clarified. We investigated a mechanism to promote insulinotropic action by means of exendin-4 and exercise training in 90% pancreatectomized (Px) rats fed 40% energy fat diets. Px diabetic rats were divided into 4 groups: 1) exendin-4, 2) exendin-4 plus exercise, 3) saline (control), and 4) exercise. During the 8-week experimental period, rats in the exendin-4 groups were subcutaneously administered with 150 pmol/kg exendin-4 twice a day, while those in the exercise groups ran on an uphill treadmill with a 15 degree incline at 20 m/min for 30 min 5 days a week. First phase insulin secretion was elevated by both the administration of exendin-4 and exercise training during hyperglycemic clamp. However, second phase insulin secretion did not differ among the groups. Individual treatment of exendin-4 and exercise expanded beta-cell mass by increasing its proliferation and reducing its apoptosis, but the administration of exendin-4 plus exercise training did not produce any additional, positive effects. Both exendin-4 and exercise enhanced insulin receptor substrate (IRS)-2 expression through the activation of cAMP responding element binding protein in the islets, which potentiated their insulin/insulin like growth factor-1 signaling. The potentiation of the signaling increased the expression of pancreas duodenum homeobox-1, involved in beta-cell proliferation. In conclusion, exendin-4 and exercise equivalently improved glucose homeostasis due to the induction of IRS-2 in the islets of diabetic rats through a cAMP dependent common pathway.
据报道，艾塞那肽-4和运动都可通过增强促胰岛素作用来改善葡萄糖稳态，但其分子机制的本质尚未阐明。我们研究了在喂食40%能量脂肪饮食的90%胰腺切除（Px）大鼠中，通过艾塞那肽-4和运动训练促进促胰岛素作用的机制。Px糖尿病大鼠分为4组：1）艾塞那肽-4组，2）艾塞那肽-4加运动组，3）生理盐水（对照组），4）运动组。在为期8周的实验期内，艾塞那肽-4组大鼠每天皮下注射150 pmol/kg艾塞那肽-4两次，而运动组大鼠每周5天在坡度为15度的上坡跑步机上以20 m/min的速度跑30分钟。在高血糖钳夹期间，艾塞那肽-4给药和运动训练均可提高第一阶段胰岛素分泌。然而，第二阶段胰岛素分泌在各组之间没有差异。单独使用艾塞那肽-4和运动通过增加β细胞增殖和减少其凋亡来扩大β细胞质量，但艾塞那肽-4加运动训练并未产生任何额外的积极效果。艾塞那肽-4和运动均通过激活胰岛中的cAMP反应元件结合蛋白来增强胰岛素受体底物（IRS）-2的表达，从而增强其胰岛素/胰岛素样生长因子-1信号传导。信号传导的增强增加了参与β细胞增殖的胰腺十二指肠同源盒-1的表达。总之，艾塞那肽-4和运动通过cAMP依赖性共同途径诱导糖尿病大鼠胰岛中的IRS-2，从而等效地改善葡萄糖稳态。
