机构：[1]Department of General Surgery, XuanWu Hospital, Capital Medical University, Beijing 100053, China普通外科首都医科大学宣武医院[2]National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China[3]The State Key Laboratory of Biomembrane and Membrane Biotechnology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing 100871, China[4]Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, USA
Upon glucose elevation, pancreatic beta-cells secrete insulin in a Ca2+-dependent manner. In diabetic animal models, different aspects of the calcium signaling pathway in beta-cells are altered, but there is no consensus regarding their relative contributions to the development of beta-cell dysfunction. In this study, we compared the increase in cytosolic Ca2+ ([Ca2+](i)) via Ca2+ influx, Ca2+ mobilization from endoplasmic reticulum (ER) calcium stores, and the removal of Ca2+ via multiple mechanisms in beta-cells from both diabetic db/db mice and non-diabetic C57BL/6J mice. We refined our previous quantitative model to describe the slow [Ca2+](i) recovery after depolarization in beta-cells from db/db mice. According to the model, the activity levels of the two subtypes of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) pump, SERCA2 and SERCA3, were severely down-regulated in diabetic cells to 65% and 0% of the levels in normal cells. This down-regulation may lead to a reduction in the Ca2+ concentration in the ER, a compensatory up-regulation of the plasma membrane Na+/Ca2+ exchanger (NCX) and a reduction in depolarization-evoked Ca2+ influx. As a result, the patterns of glucose-stimulated calcium oscillations were significantly different in db/db diabetic beta-cells compared with normal cells. Overall, quantifying the changes in the calcium signaling pathway in db/db diabetic beta-cells will aid in the development of a disease model that could provide insight into the adaptive transformations of beta-cell function during diabetes development.
基金：
the National Basic Research Program (973 Program) (No. 2013CB531200)
the National Key Technology R&D Program (No. SQ2011SF11B01041)
National NaturalScience FoundationofChina (GrantNos. 31221002and 81222020)
the Beijing Natural Science Foundation (Nos. 7121008 and 7142071)
the Basic and Clinical Research Fund of Capital Medical University (No.13JL19)
the Talents Project of Department of Beijing Municipal Party Committee Organization of the Communist Party of China (No.2011D005018000004)
the U.S. National Institutes of Health(GM83913)
第一作者机构：[1]Department of General Surgery, XuanWu Hospital, Capital Medical University, Beijing 100053, China
通讯作者：
通讯机构：[1]Department of General Surgery, XuanWu Hospital, Capital Medical University, Beijing 100053, China[3]The State Key Laboratory of Biomembrane and Membrane Biotechnology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing 100871, China
推荐引用方式(GB/T 7714)：
Kuo Liang,Wen Du,Jingze Lu,et al.Alterations of the Ca2+ signaling pathway in pancreatic beta-cells isolated from db/db mice[J].PROTEIN & CELL.2014,5(10):783-794.doi:10.1007/s13238-014-0075-7.
APA：
Kuo Liang,Wen Du,Jingze Lu,Fei Li,Lu Yang...&Liangyi Chen.(2014).Alterations of the Ca2+ signaling pathway in pancreatic beta-cells isolated from db/db mice.PROTEIN & CELL,5,(10)
MLA：
Kuo Liang,et al."Alterations of the Ca2+ signaling pathway in pancreatic beta-cells isolated from db/db mice".PROTEIN & CELL 5..10(2014):783-794
