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.
Highlights
Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance [1,2] and increased level of blood glucose concentration has been proposed to induce β-cell loss in T2D [2,3,4]
The result of tunel staining indicated that nifedipine prevented high glucose-induced INS-1 cell apoptosis (Figure 1C)
It suggested that inhibition of calcium influx by L-type-Ca2+-channel antagonist could provide benefit to prevent high glucose-induced β-cell apoptosis
Summary
Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance [1,2] and increased level of blood glucose concentration has been proposed to induce β-cell loss in T2D [2,3,4]. Cytochrome c release, caspase 3 activation might be the main cause of cell death [3,8]. The molecular and cellular mechanisms of high concentration glucose-induced β-cell apoptosis have not been well investigated. Some stress occurrence was involved in high glucose-induced β-cell dysfunction, including oxidation stress, vasoactive cytokines release, barrier function changes, and endoplasmic reticulum (ER) stress [9,10,11]. Apoptotic ER stress was demonstrated to be critical in high glucose-induced β-cell apoptosis [12,13]
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