CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake

Melita Vidakovic, Ernesto Caballero Garrido, Mirjana Mihailovic, Jelena Arambasic Jovanovic, Marija Sinadinovic, Jovana Rajic, Aleksandra Uskokovic, Svetlana Dinic, Nevena Grdovic, Milos Djordjevic, Anja Tolic, Goran Poznanovic

Abstract


We examined whether CXCL12α 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 CXCL12α prior to exposure to 7.5 µM hydrogen peroxide, which served to induce oxidative stress. Incubation of islets with CXCL12α induced pancreatic β-cell proliferation and improved the ability of β-cells to withstand oxidative stress. Consecutive treatments of isolated islets with hydrogen peroxide caused a decline in β-cell functioning over time, while the CXCL12α 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 CXCL12α 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 CXCL12α 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 CXCL12α could help to remove preexisting glucotoxicity and associated temporary β-cell stunning that might be present at the time of diabetes diagnosis in vivo.

https://doi.org/10.2298/ABS170711040V

Received: July 11, 2017; Revised: October 23, 2017; Accepted: October 24, 2017; Published online: October 30, 2017

How to cite this article: Vidaković M, Garrido EC, Mihailović M, Arambašić-Jovanović J, Sinadinović M, Rajić J, Uskoković A, Dinić S, Grdović N, Đorđević M, Tolić A, Poznanović G. CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake. Arch Biol Sci. 2018;70(1):191-204.


Keywords


diabetes; calcium; CXC chemokine ligand 12α; insulin; pancreatic islet cells; voltage-gated calcium channels

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