Vitamin D Receptor Overexpression in β-Cells Ameliorates Diabetes in Mice

Diabetes. 2020 May;69(5):927-939. doi: 10.2337/db19-0757. Epub 2020 Feb 21.

Abstract

Vitamin D deficiency has been associated with increased incidence of diabetes, both in humans and in animal models. In addition, an association between vitamin D receptor (VDR) gene polymorphisms and diabetes has also been described. However, the involvement of VDR in the development of diabetes, specifically in pancreatic β-cells, has not been elucidated yet. Here, we aimed to study the role of VDR in β-cells in the pathophysiology of diabetes. Our results indicate that Vdr expression was modulated by glucose in healthy islets and decreased in islets from both type 1 diabetes and type 2 diabetes mouse models. In addition, transgenic mice overexpressing VDR in β-cells were protected against streptozotocin-induced diabetes and presented a preserved β-cell mass and a reduction in islet inflammation. Altogether, these results suggest that sustained VDR levels in β-cells may preserve β-cell mass and β-cell function and protect against diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose
  • Diabetes Mellitus
  • Diabetes Mellitus, Experimental
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Glucose / administration & dosage
  • Glucose / pharmacology
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism*
  • Insulin-Secreting Cells / metabolism*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism*

Substances

  • Blood Glucose
  • IGF2 protein, mouse
  • Receptors, Calcitriol
  • Insulin-Like Growth Factor II
  • Glucose