We investigated intracellular Ca2+ ([Ca2+]i) oscillations evoked by glucagon-like peptide 1 (GLP-1) in relation to the ryanodine receptor (RyR) and Ca2+-induced Ca2+ release (CICR) mechanism in pancreatic B cell HIT. GLP-1 produced [Ca2+]i oscillations in the cells, both in media with and without Ca2+, an effect inhibited by ruthenium red and mimicked by 8-Br-cAMPS. In addition, the GLP-1-evoked [Ca2+]i rise was initiated at the local intercellular peripheral cytoplasm, and a resultant expansion of the intercellular space was also observed. Caffeine induced [Ca2+]i elevation in the medium with or without Ca2+, an effect inhibited by ruthenium red. GLP-1-evoked [Ca2+]i oscillations were also enhanced by IBMX, and eliminated by Rp-8-Br-cAMPS or 20 μM H-89 treatments whereas they were unaffected by 2 μM H-89 treatment. Forskolin caused a transient elevation in [Ca2+]i that was reduced by Rp-8-Br-cAMPS, 2 μM or 20 μM H-89. Our results indicate that GLP-1 initially generated a local [Ca2+]i elevation at the peripheral cytoplasm, subsequently producing [Ca2+]i oscillations that were inhibited by ruthenium red, involving ryanodine-sensitive and cAMP-activated CICR mechanisms. The cytoplasmic levels of cAMP as well as local Ca2+ might be responsible for [Ca2+]i oscillations.
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