Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
Peptides. 2011 Aug;32(8):1634-9. doi: 10.1016/j.peptides.2011.06.025. Epub 2011 Jul 5.
Apelin, a newly identified bioactive adipokine, has been found to play important roles in multiple diseases, including diabetes, hypertension and cardiovascular diseases with unclear molecular mechanisms. The present study aimed to investigate the effects of apelin on endoplasmic reticulum (ER) stress in the pancreas of Akita mice, a well-established type 1 diabetic model. Apelin-13 (400 pmol/kg) was injected from tail vein for 10 weeks. The physiological characters of experimental animals were evaluated, pancreatic islet morphology and insulin content were assessed by immunohistochemistry, and ER stress markers in the pancreas were examined by Western blots. Our results indicate apelin treatment significantly ameliorates diabetes-induced reduction in pancreatic islet mass and insulin content. Further studies suggested apelin treatment alleviates ER stress by inhibiting the diabetes induced up-regulation of PERK and IRE1α and chaperones (GRP78, calnexin and Hsp70) levels in Akita mice. We also demonstrated that apelin treatment normalizes the diabetes induced alteration of AKT and ERK activations in the pancreas of Akita mice. Taken together, these results suggest a novel physiological role of apelin in alleviating ER stress in the pancreas of type 1 diabetes.
Apelin，一种新发现的生物活性脂肪因子，已被发现在多种疾病中发挥重要作用，包括糖尿病、高血压和心血管疾病，但分子机制尚不清楚。本研究旨在探讨 Apelin 对 Akita 小鼠（一种成熟的 1 型糖尿病模型）胰腺内质网（ER）应激的影响。Apelin-13（400 pmol/kg）经尾静脉注射 10 周。通过免疫组织化学评估实验动物的生理特征，评估胰腺胰岛形态和胰岛素含量，并通过 Western blot 检测胰腺 ER 应激标志物。我们的结果表明，Apelin 治疗可显著改善糖尿病引起的胰岛质量和胰岛素含量减少。进一步的研究表明，Apelin 治疗通过抑制糖尿病诱导的 PERK 和 IRE1α以及伴侣蛋白（GRP78、钙连蛋白和 Hsp70）水平的上调，减轻了 ER 应激。我们还表明，Apelin 治疗可使糖尿病诱导的 Akita 小鼠胰腺中 AKT 和 ERK 激活的改变恢复正常。总之，这些结果表明 Apelin 在缓解 1 型糖尿病胰腺 ER 应激方面具有新的生理作用。
