Glucose-Dependent Insulin Secretion in Pancreatic β-Cell Islets from Male Rats Requires Ca2+ Release via ROS-Stimulated Ryanodine Receptors

• DOI: 10.1371/journal.pone.0129238
• Publication Date: 2015-06-05T19:03:20Z
• Authors: Paola Llanos; Ariel Contreras-F...; Genaro Barrientos; Marco Valencia; David Mears; Cecilia Hidalgo
• Keywords: Pancreatic Islets

Glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells requires an increase in intracellular free Ca2+ concentration ([Ca2+]). Glucose uptake into promotes influx and reactive oxygen species (ROS) generation. In other cell types, ROS jointly induce release mediated by ryanodine receptor (RyR) channels. Therefore, we explored here if RyR-mediated contributes to GSIS β-cell islets isolated male rats. Stimulatory glucose increased islet secretion, promoted generation dissociated β-cells. Conventional PCR assays immunostaining confirmed that express RyR2, the cardiac RyR isoform. Extended incubation of with inhibitory suppressed GSIS; so did antioxidant N-acetyl cysteine (NAC), which also decreased induced plus caffeine. Inhibitory or NAC not affect carbachol, engages inositol 1,4,5-trisphosphate receptors. Incubation H2O2 basal 2-fold. significantly H2O2-stimulated prevented 4.5-fold cytoplasmic [Ca2+] produced H2O2. Addition stimulatory (in glucose) disaggregated RyR2 S-glutathionylation similar levels, measured a proximity ligation assay; contrast, reduced glucose. We propose RyR2-mediated release, concomitant increases glucose, is essential step GSIS.