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Secretagogue-induced [Ca2+]i changes in single rat pancreatic islets and correlation with simultaneously measured insulin release
in Journal of Molecular EndocrinologyABSTRACT
The effects of secretagogues (glucose, tolbutamide and phorbol esters) on simultaneously measured intracellular free calcium concentration ([Ca2+]i) and insulin release were studied in rat pancreatic islets of Langerhans. Stimulatory concentrations (11 mm) of glucose caused a transient [Ca2+]i increase followed by an almost flat second phase. Increasing glucose concentrations to 16·7 mm in steps caused a further increase in [Ca2+]i. In contrast with mouse islets, rat islets scarcely showed glucose-induced [Ca2+]i oscillations. Digital image analysis showed that [Ca2+]i changes occurred synchronously across the whole islet. As expected, simultaneously measured insulin release was biphasic with a clear second phase. This clearly indicated that in rat islets there is a lack of correlation between [Ca2+]i and insulin release. This was further explored using agents which separately promoted the first (tolbutamide, 200 μm) and second (phorbol-12-myristate-13-acetate; PMA; 5 nm) phases of insulin release. Tolbutamide induced a transient increase in [Ca2+]i paralleled by a transient increase in insulin release, whereas PMA induced a slow increase in insulin release without a clear change in [Ca2+]i. These results suggest that in rat islets the first phase of insulin release is calcium dependent, whereas the second phase is related to the activation of protein kinase C (PKC). However, the glucose-induced second phase of insulin release did not coincide with an increase in membrane-associated PKC activity. Other messengers may contribute to this late phase of insulin release.
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Online ISSN: 1479-6813
Print ISSN: 0952-5041
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