BIOTEC TU-Dresden, Tatzberg 47/49 01307, Germany.
Alberta Diabetes Institute and Department of Pharmacology, University of Alberta, Edmonton T6G 2E1, AB, Canada.
Biomolecules. 2012 May 24;2(2):269-81. doi: 10.3390/biom2020269.
The secretion of insulin by pancreatic islet β-cells plays a pivotal role in glucose homeostasis and diabetes. Recent work suggests an important role for SUMOylation in the control of insulin secretion from β-cells. In this paper we discuss mechanisms whereby (de)SUMOylation may control insulin release by modulating β-cell function at one or more key points; and particularly through the acute and reversible regulation of the exocytotic machinery. Furthermore, we postulate that the SUMO-specific protease SENP1 is an important mediator of insulin exocytosis in response to NADPH, a metabolic secretory signal and major determinant of β-cell redox state. Dialysis of mouse β-cells with NADPH efficiently amplifies β-cell exocytosis even when extracellular glucose is low; an effect that is lost upon knockdown of SENP1. Conversely, over-expression of SENP1 itself augments β-cell exocytosis in a redox-dependent manner. Taken together, we suggest that (de)SUMOylation represents an important mechanism that acutely regulates insulin secretion and that SENP1 can act as an amplifier of insulin exocytosis.
胰岛β细胞分泌的胰岛素在葡萄糖稳态和糖尿病中起着关键作用。最近的研究表明，SUMO 化在控制β细胞胰岛素分泌中起着重要作用。本文讨论了（去）SUMO 化可能通过调节β细胞功能在一个或多个关键点控制胰岛素释放的机制；特别是通过对胞吐机制的急性和可逆调节。此外，我们假设 SUMO 特异性蛋白酶 SENP1 是 NADPH 作为代谢分泌信号和β细胞氧化还原状态主要决定因素，对胰岛素胞吐作用的重要介导物。用 NADPH 对小鼠β细胞进行透析可有效放大β细胞胞吐作用，即使细胞外葡萄糖水平较低；当 SENP1 被敲低时，这种作用就会消失。相反，SENP1 的过表达本身以依赖于氧化还原的方式增强β细胞的胞吐作用。综上所述，我们认为（去）SUMO 化代表了一种急性调节胰岛素分泌的重要机制，而 SENP1 可以作为胰岛素胞吐作用的放大器。
