Q. Cheng, Y. C. Li, Barbara J. Boucher
Mar 20, 2011
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Influential Citations
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Journal
Diabetologia
Abstract
Aims/hypothesisThe aim of this study was to demonstrate that hormonal vitamin D (calcitriol) modulates the local pancreatic islet renin-angiotensin system (RAS) whilst improving islet beta cell secretory function.MethodsIsolated islets cultured ex vivo under high- or low-glucose conditions and treated with or without calcitriol were examined for changes in RAS component activity and glucose-stimulated insulin secretion (GSIS). Isolated islets from vitamin D receptor knockout (VDR-KO) mice were compared with islets from wild-type (WT) mice for major RAS component expression and RAS protein production.ResultsIsolated islets incubated ex vivo under high-glucose conditions showed increased expression and production of major RAS components; this was prevented and reversed by calcitriol in parallel with increases in GSIS. VDR-KO mice displayed increased RAS component mRNA expression and protein production as compared with WT mice, despite comparable glucose homeostasis.ConclusionsYoung mice with vitamin D receptor ablation showed abnormal increases in islet RAS components at mRNA and protein levels, despite unaltered glucose homeostasis. Calcitriol prevents and can correct induction of RAS component production under high-glucose conditions in parallel with the well-known effect of calcitriol on increasing islet beta cell secretory responses to glucose.