Alterations of the Ca<sup>2+</sup> signaling pathway in pancreatic beta-cells isolated from db/db mice

doi:10.1007/s13238-014-0075-7

Protein Cell

2014, Vol. 5

Issue (10) : 783-794 https://doi.org/10.1007/s13238-014-0075-7

RESEARCH ARTICLE

Alterations of the Ca²⁺ signaling pathway in pancreatic beta-cells isolated from db/db mice

Kuo Liang¹,Wen Du²,Jingze Lu²,Fei Li^1,^*(

),Lu Yang³,Yanhong Xue²,Bertil Hille⁴,Liangyi Chen^3,^*(

)

1. Department of General Surgery, XuanWu Hospital, Capital Medical University, Beijing 100053, China
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

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Abstract

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 nondiabetic 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 depolarizationevoked Ca²⁺ influx. As a result, the patterns of glucosestimulated 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.

Keywords diabetic beta-cells calcium signaling alterations SERCA pump db/db mice

Corresponding Author(s): Fei Li

Issue Date: 24 October 2014

Cite this article:

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.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-014-0075-7
https://academic.hep.com.cn/pac/EN/Y2014/V5/I10/783

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