The ellagitannin metabolite urolithin C is a glucose-dependent regulator of insulin secretion through activation of L-type calcium channels

British Journal of Pharmacology
Morgane BayleCatherine Oiry

Abstract

The pharmacology of polyphenol metabolites on beta-cell function is largely undetermined. We sought to identify polyphenol metabolites that enhance the insulin-secreting function of beta-cells and to explore the underlying mechanisms. INS-1 beta-cells and rat isolated islets of Langerhans or perfused pancreas preparations were used for insulin secretion experiments. Molecular modelling, intracellular Ca2+ monitoring, and whole-cell patch-clamp recordings were used for mechanistic studies. Among a set of polyphenol metabolites, we found that exposure of INS-1 beta-cells to urolithins A and C enhanced glucose-stimulated insulin secretion. We further characterized the activity of urolithin C and its pharmacological mechanism. Urolithin C glucose-dependently enhanced insulin secretion in isolated islets of Langerhans and perfused pancreas preparations. In the latter, enhancement was reversible when glucose was lowered from a stimulating to a non-stimulating concentration. Molecular modelling suggested that urolithin C could dock into the Cav 1.2 L-type Ca2+ channel. Calcium monitoring indicated that urolithin C had no effect on basal intracellular Ca2+ but enhanced depolarization-induced increase in intracellular Ca2+ in INS-1 cell...Continue Reading

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Citations

Feb 23, 2020·Fundamental & Clinical Pharmacology·Slimane ToubalJérémie Neasta
Apr 14, 2020·International Journal of Food Sciences and Nutrition·Margherita Dall'AstaFurio Brighenti
Jun 8, 2021·Frontiers in Endocrinology·Qing FangDongsheng Ouyang
Sep 21, 2021·Phytotherapy Research : PTR·Seyyed Hossein HasheminezhadMilad Iranshahy

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