Aslamy Arianne, Thurmond Debbie C
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; and.
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; and
Am J Physiol Regul Integr Comp Physiol. 2017 May 1;312(5):R739-R752. doi: 10.1152/ajpregu.00002.2017. Epub 2017 Mar 29.
Diabetes remains one of the leading causes of morbidity and mortality worldwide, affecting an estimated 422 million adults. In the US, it is predicted that one in every three children born as of 2000 will suffer from diabetes in their lifetime. Type 2 diabetes results from combinatorial defects in pancreatic β-cell glucose-stimulated insulin secretion and in peripheral glucose uptake. Both processes, insulin secretion and glucose uptake, are mediated by exocytosis proteins, SNARE (soluble -ethylmaleimide-sensitive factor attachment protein receptor) complexes, Sec1/Munc18 (SM), and double C2-domain protein B (DOC2B). Increasing evidence links deficiencies in these exocytosis proteins to diabetes in rodents and humans. Given this, emerging studies aimed at restoring and/or enhancing cellular levels of certain exocytosis proteins point to promising outcomes in maintaining functional β-cell mass and enhancing insulin sensitivity. In doing so, new evidence also shows that enhancing exocytosis protein levels may promote health span and longevity and may also harbor anti-cancer and anti-Alzheimer's disease capabilities. Herein, we present a comprehensive review of the described capabilities of certain exocytosis proteins and how these might be targeted for improving metabolic dysregulation.
糖尿病仍然是全球发病和死亡的主要原因之一，影响着约4.22亿成年人。在美国，预计2000年以后出生的儿童中，每三人就有一人一生中会患糖尿病。2型糖尿病是由胰腺β细胞葡萄糖刺激的胰岛素分泌和外周葡萄糖摄取的组合缺陷引起的。胰岛素分泌和葡萄糖摄取这两个过程均由胞吐蛋白、SNARE（可溶性N - 乙基马来酰亚胺敏感因子附着蛋白受体）复合物、Sec1/Munc18（SM）和双C2结构域蛋白B（DOC2B）介导。越来越多的证据表明，这些胞吐蛋白的缺陷与啮齿动物和人类的糖尿病有关。鉴于此，旨在恢复和/或提高某些胞吐蛋白细胞水平的新研究表明，在维持功能性β细胞数量和提高胰岛素敏感性方面可能会有良好的结果。与此同时，新证据还表明，提高胞吐蛋白水平可能会促进健康寿命和延长寿命，还可能具有抗癌和抗阿尔茨海默病的能力。在此，我们全面综述了某些胞吐蛋白的上述功能，以及如何针对这些功能来改善代谢失调。
