Cytokine-mediated changes in K+ channel activity promotes an adaptive Ca2+ response that sustains β-cell insulin secretion during inflammation
| Autor: | Kelli L. Jordan, Sarah C. Milian, David A. Jacobson, Molly K. Altman, Avery M. Bogart, Prasanna K. Dadi, Matthew T. Dickerson |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Calcium metabolism geography Multidisciplinary geography.geographical_feature_category Chemistry medicine.medical_treatment Endoplasmic reticulum lcsh:R lcsh:Medicine Inflammation Islet Potassium channel Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Cytokine medicine lcsh:Q medicine.symptom lcsh:Science 030217 neurology & neurosurgery Intracellular Ion transporter |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-15 (2018) |
| ISSN: | 2045-2322 |
| Popis: | Cytokines present during low-grade inflammation contribute to β-cell dysfunction and diabetes. Cytokine signaling disrupts β-cell glucose-stimulated Ca2+ influx (GSCI) and endoplasmic reticulum (ER) Ca2+ ([Ca2+]ER) handling, leading to diminished glucose-stimulated insulin secretion (GSIS). However, cytokine-mediated changes in ion channel activity that alter β-cell Ca2+ handling remain unknown. Here we investigated the role of K+ currents in cytokine-mediated β-cell dysfunction. Kslow currents, which control the termination of intracellular Ca2+ ([Ca2+]i) oscillations, were reduced following cytokine exposure. As a consequence, [Ca2+]i and electrical oscillations were accelerated. Cytokine exposure also increased basal islet [Ca2+]i and decreased GSCI. The effect of cytokines on TALK-1 K+ currents were also examined as TALK-1 mediates Kslow by facilitating [Ca2+]ER release. Cytokine exposure decreased KCNK16 transcript abundance and associated TALK-1 protein expression, increasing [Ca2+]ER storage while maintaining 2nd phase GSCI and GSIS. This adaptive Ca2+ response was absent in TALK-1 KO islets, which exhibited decreased 2nd phase GSCI and diminished GSIS. These findings suggest that Kslow and TALK-1 currents play important roles in altered β-cell Ca2+ handling and electrical activity during low-grade inflammation. These results also reveal that a cytokine-mediated reduction in TALK-1 serves an acute protective role in β-cells by facilitating increased Ca2+ content to maintain GSIS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|