We examined whether CXCL12? improves insulin secretion by influencing the Ca2+ oscillation pattern and Ca2+ influx ([Ca2+]i), thereby enhancing the viability of pancreatic islet cells in oxidative stress. The islets of Langerhans were isolated from male OF1 mice and pretreated with 40 ng/mL of CXCL12? prior to exposure to 7.5 ?M hydrogen peroxide, which served to induce oxidative stress. Incubation of islets with CXCL12? induced pancreatic ?-cell proliferation and improved the ability of ?-cells to withstand oxidative stress. Consecutive treatments of isolated islets with hydrogen peroxide caused a decline in ?-cell functioning over time, while the CXCL12? pretreatment of islets exhibited a physiological response to high glucose that was comparable to control islets. The attenuated response of islets to a high D-glucose challenge was observed as a partial to complete abolishment of [Ca2+]i. Treatments with increasing concentrations of CXCL12? decreased the number of Ca2+ oscillations that lasted longer, thus pointing to an overall increase in [Ca2+]i, which was followed by increased insulin secretion. In addition, treatment of islets with CXCL12? enhanced the transcription rate for insulin and the CXCR4 gene, pointing to the importance of CXCL12/CXCR4 signaling in the regulation of Ca2+ intake and insulin secretion in pancreatic islet cells. We propose that a potential treatment with CXCL12? could help to remove preexisting glucotoxicity and associated temporary ?-cell stunning that might be present at the time of diabetes diagnosis in vivo.
Oxidative stress induces p21 expression in pancreatic islet cells: possible implication in beta-cell dysfunction