Glucose activates prenyltransferases in pancreatic islet β-cells
Glucose activates prenyltransferases in pancreatic islet β-cells
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DOI：
10.1016/j.bbrc.2009.11.159
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发表时间：
2010-01-01
影响因子：
3.1
通讯作者：
Kowluru, Anjaneyulu
中科院分区：
文献类型：
--
作者：
Goalstione, Marc;Kamath, Vasudeva;Kowluru, Anjaneyulu
越来越多的证据表明小G蛋白[如Cdc 42和Rac 1]参与胰岛β细胞中葡萄糖刺激的胰岛素分泌[GSIS]。这些信号蛋白在其C-末端半胱氨酸残基处经历翻译后修饰[例如，异戊二烯化]，并且似乎对于含胰岛素的分泌颗粒与质膜的转运和融合以及胰岛素的胞吐分泌是必需的。然而，迄今为止尚未研究生理性胰岛素分泌物[例如葡萄糖]对异戊二烯化酶的潜在调节。本文所我们报告免疫定位。法尼基转移酶[FT酶]和香叶基香叶基转移酶[GGT酶]的亚细胞分布和葡萄糖在胰岛素分泌的INS 832/13 β-细胞和正常大鼠胰岛中的调节我们的发现表明促胰岛素浓度的葡萄糖[20 mM]显著刺激了FT酶/GGT酶-1的α-亚单位的表达。而不是FTase或GGT酶-1的β-亚基，而不显著影响INS 832/13细胞和啮齿动物胰岛中这些全酶的主要胞质分布。在这些条件下，葡萄糖显著刺激两种细胞类型中FTase和GGT酶-1的活性[比基础高2.5- 4.0倍]。总之，这些发现提供了第一个证据，表明GSIS涉及葡萄糖激活内源性胰岛异戊二烯基转移酶，最终激活其各自的G蛋白底物，这是细胞骨架重排，囊泡运输，融合和胰岛素分泌所必需的。
A growing body of evidence implicates small G-proteins [e.g, Cdc42 and Rac1] in glucose-stimulated insulin secretion [GSIS] in the islet beta-cell. These signaling proteins undergo post-translational modifications [e g, prenylation] at their C-terminal cysteine residue and appear to be essential for the transport and fusion of insulin-containing secretary granules with the plasma membrane and the exocytotic secretion of insulin. However, potential regulation of the prenylating enzymes by physiological Insulin secretogues [e.g. glucose] has not been investigated thus far. Herein. we report immunological localization. sub-cellular distribution and regulation of farnesyltransferases [FTases] and geranylgeranyltransferase [GGTase] by glucose in insulin-secreting INS 832/13 beta-cells and normal rat islets Our findings suggest that an insulinotropic concentration of glucose [20 mM] markedly stimulated the expression of the alpha-subunits of FTase/GGTase-1. but not the beta-subunits of FTase or GGTase-1 without significantly affecting the predominantly cytosolic distribution of these holoenzymes in INS 832/13 cells and rodent islets Under these conditions, glucose significantly stimulated [2.5- to 4.0-fold over basal] the activities of both FTase and GGTase-1 in both cell types. Together, these findings provide the first evidence to Suggest that GSIS involves activation of the endogenous islet prenyltransferases by glucose, Culminating in the activation of their respective G-protein substrates, which is necessary for cytoskeletal rearrangement, vesicular transport, fusion and secretion of insulin Published by Elsevier Inc