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
2018
Preuzimanje 🢃
Autori:
Vidaković, MelitaMihailović, Mirjana
Đorđević, Marija
Rajić, Jovana
Uskoković, Aleksandra
Dinić, Svetlana
Grdović, Nevena
Đorđević, Miloš
Tolić, Anja
Poznanović, Goran
Caballero, Garrido
Arambašić Jovanović, Jelena
Tip dokumenta:
Članak u časopisu (Recenzirana verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
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.
Ključne reči:
Diabetes; Calcium; CXC chemokine ligand 12α; Insulin; Pancreatic islet cells; Voltage-gated calcium channelsIzvor:
Archives of Biological Sciences, 2018, 70, 1, 191-204Finansiranje / projekti:
- Signalni molekuli u dijabetesu: identifikacija potencijalnih bioloških markera uključenih u modifikaciju i integraciju signalnih puteva u cilju predikcije i intervencije u dijabetesu (RS-MESTD-Basic Research (BR or ON)-173020)
Povezane informacije:
- Druga verzija
https://radar.ibiss.bg.ac.rs/handle/123456789/3023
DOI: 10.2298/ABS170711040V
ISSN: 0354-4664
WoS: 000428370100019
Scopus: 2-s2.0-85043718185
URI
http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46641700040Vhttps://radar.ibiss.bg.ac.rs/handle/123456789/2886