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
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 CXCL1...
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University of Belgrade, University of Novi Sad
2018-01-01
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Series: | Archives of Biological Sciences |
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Online Access: | http://www.doiserbia.nb.rs/img/doi/0354-4664/2018/0354-46641700040V.pdf |
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author | Vidaković Melita Caballero-Garrido Ernesto Mihailović Mirjana Arambašić-Jovanović Jelena Sinadinović Marija Rajić Jovana Uskoković Aleksandra Dinić Svetlana Grdović Nevena Đorđević Miloš Tolić Anja Poznanović Goran |
author_facet | Vidaković Melita Caballero-Garrido Ernesto Mihailović Mirjana Arambašić-Jovanović Jelena Sinadinović Marija Rajić Jovana Uskoković Aleksandra Dinić Svetlana Grdović Nevena Đorđević Miloš Tolić Anja Poznanović Goran |
author_sort | Vidaković Melita |
collection | DOAJ |
description | 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. [Project of the Serbian Ministry of Education, Science and
Technological Development, Grant no. 173020] |
first_indexed | 2024-12-10T18:58:01Z |
format | Article |
id | doaj.art-1aa508f2027f469c9ee47d0ac02ec823 |
institution | Directory Open Access Journal |
issn | 0354-4664 1821-4339 |
language | English |
last_indexed | 2024-12-10T18:58:01Z |
publishDate | 2018-01-01 |
publisher | University of Belgrade, University of Novi Sad |
record_format | Article |
series | Archives of Biological Sciences |
spelling | doaj.art-1aa508f2027f469c9ee47d0ac02ec8232022-12-22T01:37:05ZengUniversity of Belgrade, University of Novi SadArchives of Biological Sciences0354-46641821-43392018-01-0170119120410.2298/ABS170711040V0354-46641700040VCXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptakeVidaković Melita0Caballero-Garrido Ernesto1Mihailović Mirjana2Arambašić-Jovanović Jelena3Sinadinović Marija4Rajić Jovana5Uskoković Aleksandra6Dinić Svetlana7Grdović Nevena8Đorđević Miloš9Tolić Anja10Poznanović Goran11Institute for Biological Research, Department of Molecular Biology, Belgrade + Universidad Miguel Hernández de Elche, Institute of Bioengineering, UNIT of Cell Physiology and Nutrition, Elche, SpainUniversidad Miguel Hernández de Elche, Institute of Bioengineering, UNIT of Cell Physiology and Nutrition, Elche, SpainInstitute for Biological Research, Department of Molecular Biology, BelgradeInstitute for Biological Research, Department of Molecular Biology, BelgradeInstitute for Biological Research, Department of Molecular Biology, BelgradeInstitute for Biological Research, Department of Molecular Biology, BelgradeInstitute for Biological Research, Department of Molecular Biology, BelgradeInstitute for Biological Research, Department of Molecular Biology, BelgradeInstitute for Biological Research, Department of Molecular Biology, BelgradeInstitute for Biological Research, Department of Molecular Biology, BelgradeInstitute for Biological Research, Department of Molecular Biology, BelgradeInstitute for Biological Research, Department of Molecular Biology, BelgradeWe 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. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173020]http://www.doiserbia.nb.rs/img/doi/0354-4664/2018/0354-46641700040V.pdfdiabetescalciumCXC chemokine ligand 12αinsulinpancreatic islet cellsvoltage-gated calcium channels |
spellingShingle | Vidaković Melita Caballero-Garrido Ernesto Mihailović Mirjana Arambašić-Jovanović Jelena Sinadinović Marija Rajić Jovana Uskoković Aleksandra Dinić Svetlana Grdović Nevena Đorđević Miloš Tolić Anja Poznanović Goran 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 Archives of Biological Sciences diabetes calcium CXC chemokine ligand 12α insulin pancreatic islet cells voltage-gated calcium channels |
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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | diabetes calcium CXC chemokine ligand 12α insulin pancreatic islet cells voltage-gated calcium channels |
url | http://www.doiserbia.nb.rs/img/doi/0354-4664/2018/0354-46641700040V.pdf |
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