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Nifedipine Protects INS-1 β-Cell from High Glucose-Induced ER Stress and Apoptosis
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Southeast University, No.87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China
Key Laboratory of Human Functional Genomics of Jiangsu Province, Clinical Diabetes Centre of Jiangsu Province, Nanjing Medical University, Nanjing 210029, China
* Author to whom correspondence should be addressed.
Received: 30 August 2011; in revised form: 19 October 2011 / Accepted: 31 October 2011 / Published: 7 November 2011
Abstract: Sustained high concentration of glucose has been verified toxic to β-cells. Glucose augments Ca2+-stimulated insulin release in pancreatic β-cells, but chronic high concentration of glucose could induce a sustained level of Ca2+ in β-cells, which leads to cell apoptosis. However, the mechanism of high glucose-induced β-cell apoptosis remains unclear. In this study, we use a calcium channel blocker, nifedipine, to investigate whether the inhibition of intracellular Ca2+ concentration could protect β-cells from chronic high glucose-induced apoptosis. It was found that in a concentration of 33.3 mM, chronic stimulation of glucose could induce INS-1 β-cells apoptosis at least through the endoplasmic reticulum stress pathway and 10 μM nifedipine inhibited Ca2+ release to protect β-cells from high glucose-induced endoplasmic reticulum stress and apoptosis. These results indicated that inhibition of Ca2+ over-accumulation might provide benefit to attenuate islet β-cell decompensation in a high glucose environment.
Keywords: nifedipine; Ca2+ homeostasis; β-cell; endoplasmic reticulum stress; apoptosis; high glucose
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Wang, Y.; Gao, L.; Li, Y.; Chen, H.; Sun, Z. Nifedipine Protects INS-1 β-Cell from High Glucose-Induced ER Stress and Apoptosis. Int. J. Mol. Sci. 2011, 12, 7569-7580.
Wang Y, Gao L, Li Y, Chen H, Sun Z. Nifedipine Protects INS-1 β-Cell from High Glucose-Induced ER Stress and Apoptosis. International Journal of Molecular Sciences. 2011; 12(11):7569-7580.
Wang, Yao; Gao, Lu; Li, Yuan; Chen, Hong; Sun, Zilin. 2011. "Nifedipine Protects INS-1 β-Cell from High Glucose-Induced ER Stress and Apoptosis." Int. J. Mol. Sci. 12, no. 11: 7569-7580.