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- Title
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.
- Authors
Vidaković, Melita; Garrido, Ernesto Caballero; Mihailović, Mirjana; Jovanović, Jelena Arambašić; Sinadinović, Marija; Rajić, Jovana; Uskoković, Aleksandra; Dinić, Svetlana; Grdović, Nevena; Đorđević, Miloš; Tolić, Anja; Poznanović, Goran
- Abstract
We examined whether CXCL12a 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 CXCL12a prior to exposure to 7.5 µM hydrogen peroxide, which served to induce oxidative stress. Incubation of islets with CXCL12a 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 CXCL12a 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 CXCL12a 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 CXCL12a 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 CXCL12a could help to remove preexisting glucotoxicity and associated temporary β-cell stunning that might be present at the time of diabetes diagnosis in vivo.
- Subjects
CHEMOKINES; LIGANDS (Biochemistry); ISLANDS of Langerhans; PHYSIOLOGICAL effects of calcium; OXIDATIVE stress; LABORATORY mice
- Publication
Archives of Biological Sciences, 2018, Vol 70, Issue 1, p191
- ISSN
0354-4664
- Publication type
Article
- DOI
10.2298/ABS170711040V