Vitamin D Rescues Pancreatic β Cell Dysfunction due to Iron Overload via Elevation of the Vitamin D Receptor and Maintenance of Ca2+ Homeostasis

Mol Nutr Food Res. 2021 Feb;65(4):e2000772. doi: 10.1002/mnfr.202000772. Epub 2021 Jan 15.

Abstract

Scope: Accumulating evidence indicates that micronutrients are related to metabolic diseases. However, comparatively less attention has been devoted to their influence on each other during the development of metabolic diseases. To investigate the underlying mechanisms, the effects of iron and vitamin D on pancreatic β cell functions are examined.

Methods and results: Iron overload is induced in INS-1 rat insulinoma pancreatic β cells and it is found that iron overload dramatically reduce expression of the vitamin D receptor (VDR). Iron overload-induced β cell dysfunction is rescued by 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) cotreatment via restoration of VDR level and the consequent maintenance of Ca2+ homeostasis. Iron accumulation is also observed in the islets of 22-month-old C57BL/6 mice fed with a chow diet (1000 IU vitamin D3 per kg). In contrast, islet iron accumulation and hyperinsulinemia are ameliorated in mice fed with a vitamin D3 -supplemented diet (20 000 IU kg-1 ).

Conclusion: The authors show that functional failure of β cells due to iron accumulation is rescued by 1,25(OH)2 D3 , and iron overload significantly reduces VDR levels in β cells. These results suggest that iron and vitamin D inversely influence pancreatic β cell function.

Keywords: Ca2+ homeostasis; iron overload; pancreatic β cell failure; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cation Transport Proteins / metabolism
  • Cell Line
  • Cholecalciferol / pharmacology*
  • Homeostasis / drug effects
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Iron / metabolism
  • Iron Overload / drug therapy
  • Iron Overload / metabolism
  • Iron Overload / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Rats
  • Receptors, Calcitriol / metabolism*
  • Vitamin D / analogs & derivatives
  • Vitamin D / pharmacology

Substances

  • Cation Transport Proteins
  • Receptors, Calcitriol
  • dihydroxy-vitamin D3
  • solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
  • Vitamin D
  • Cholecalciferol
  • Iron
  • Calcium