A novel role for vitamin D: modulation of expression and function of the local renin-angiotensin system in mouse pancreatic islets

Diabetologia. 2011 Aug;54(8):2077-81. doi: 10.1007/s00125-011-2100-1. Epub 2011 Mar 20.

Abstract

Aims/hypothesis: The 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.

Methods: Isolated 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.

Results: Isolated 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.

Conclusions: Young 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Calcitriol / pharmacology
  • Gene Expression Regulation*
  • Glucose / pharmacology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Renin-Angiotensin System / drug effects*
  • Renin-Angiotensin System / physiology*
  • Vitamin D / pharmacology*

Substances

  • Blood Glucose
  • Receptors, Calcitriol
  • Vitamin D
  • Calcitriol
  • Glucose