GGPPS‐mediated Rab27A geranylgeranylation regulates β cell dysfunction during type 2 diabetes development by affecting insulin granule docked pool formation

• DOI: 10.1002/path.4652
• Publication Date: 2015-10-05T10:36:46Z
• Authors: Shan Jiang; Di Shen; Wen‐Jun Jia; Xiao Han; Ning Shen; Weiwei Tao; Xiang Gao; Bin Xue; Chao‐Jun Li
• Keywords: Granule (geology)

Abstract Loss of first‐phase insulin secretion associated with β cell dysfunction is an independent predictor type 2 diabetes mellitus ( T2DM ) onset. Here we found that a critical enzyme involved in protein prenylation, geranylgeranyl pyrophosphate synthase GGPPS ), required to maintain secretion. shows biphasic expression pattern islets db/db mice during the progression : increased compensatory period, followed by decrease dysfunction. Ggpps deletion cells results typical dysfunction, blunted glucose‐stimulated and consequent insufficiency. However, number size biosynthesis are unaltered. Transmission electron microscopy reduced granules adjacent cellular membrane, suggesting defect docked granule pool formation, while reserve unaffected. ablation depletes GGPP impairs Rab27A geranylgeranylation, which responsible for deficiency ‐null mice. Moreover, re‐expression or administration restore islets. These suggest ‐controlled regulates formation pool, function release development . Copyright © 2015 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.