Science：糖尿病病因新发现—基因突变
瑞典研究人员最近在研究某些糖尿病患者体内胰岛素分泌失常原因过程中发现，一种关键细胞中的基因变异导致了胰岛素分泌失常，这一发现有望为糖尿病治疗开辟新路。
胰岛素是促进合成代谢的激素，也是保证人体内血糖处于正常水平的主要激素之一。一些人之所以患上糖尿病，就是因为体内负责分泌胰岛素的胰岛β细胞不能正常发挥作用。
据此间媒体报道，卡罗林斯卡医学院研究人员发现，人体内一旦需要胰岛素供应，一种名为ＩｎｓＰ７的特殊分子便会发出增加胰岛素分泌的信号，而ＩＩ型糖尿病患者的胰腺β细胞中，负责调控这种特殊分子的基因发生了变异，从而导致胰腺β细胞不能正常分泌人体所需的胰岛素。
研究项目的负责人奥洛夫·贝里格伦教授说，这一发现具有重要意义，它给糖尿病治疗带来新思路。人们今后可以开发能修复控制ＩｎｓＰ７的基因的方法，从而促使胰腺β细胞正常分泌胰岛素。
有关研究成果发表在最新一期美国《科学》杂志上。（新华网）
原始出处:
Science 23 November 2007:
Vol. 318. no. 5854, pp. 1299 - 1302
DOI: 10.1126/science.1146824
Requirement of Inositol Pyrophosphates for Full Exocytotic Capacity in Pancreatic β Cells
Christopher Illies,1 Jesper Gromada,2 Roberta Fiume,1 Barbara Leibiger,1 Jia Yu,1 Kirstine Juhl,3 Shao-Nian Yang,1 Deb K. Barma,4 John R. Falck,4 Adolfo Saiardi,5 Christopher J. Barker,1* Per-Olof Berggren1
Inositol pyrophosphates are recognized components of cellular processes that regulate vesicle trafficking, telomere length, and apoptosis. We observed that pancreatic β cells maintain high basal concentrations of the pyrophosphate diphosphoinositol pentakisphosphate (InsP7 or IP7). Inositol hexakisphosphate kinases (IP6Ks) that can generate IP7 were overexpressed. This overexpression stimulated exocytosis of insulin-containing granules from the readily releasable pool. Exogenously applied IP7 dose-dependently enhanced exocytosis at physiological concentrations. We determined that IP6K1 and IP6K2 were present in β cells. RNA silencing of IP6K1, but not IP6K2, inhibited exocytosis, which suggests that IP6K1 is the critical endogenous kinase. Maintenance of high concentrations of IP7 in the pancreatic β cell may enhance the immediate exocytotic capacity and consequently allow rapid adjustment of insulin secretion in response to increased demand.
1 The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
2 Diabetes and Metabolism Disease Area, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
3 Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
4 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
5 U.K. Medical Research Council (MRC) Cell Biology Unit and Laboratory for Molecular Cell Biology, Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.
* To whom correspondence should be addressed. E-mail: chris.barker@ki.se
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