Effect of a transcriptional inactive or absent vitamin D receptor on beta-cell function and glucose homeostasis in mice.

Vitamin D deficiency is associated with beta-cell dysfunction and a higher risk of diabetes, but mice and humans with an absence of the vitamin D receptor (VDR) display normal glucose tolerance. Here, we investigated the direct effects of absence of VDR or absence of ligand activation of VDR on beta-cell function. For this purpose, we generated mice, with a mutation in the AF2 domain of Vdr (VDRΔAF2), preventing ligand-driven transcriptional activation of vitamin D responsive genes.

Discovery of molecular pathways mediating 1,25-dihydroxyvitamin D3 protection against cytokine-induced inflammation and damage of human and male mouse islets of Langerhans.

Protection against insulitis and diabetes by active vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), in nonobese diabetic mice has until now mainly been attributed to its immunomodulatory effects, but also protective effects of this hormone on inflammation-induced β-cell death have been reported. The aim of this study was to clarify the molecular mechanisms by which 1,25(OH)2D3 contributes to β-cell protection against cytokine-induced β-cell dysfunction and death. Human and mouse islets were exposed to IL-1β and interferon-γ in the presence or absence of 1,25(OH)2D3.

Unraveling the effects of 1,25OH2D3 on global gene expression in pancreatic islets.

Introduction: Vitamin D deficiency has been linked to type 1 and 2 diabetes, whereas supplementation may prevent both diseases. However, the extent of the effects of vitamin D or its metabolites directly on pancreatic islets is still largely unknown. The aim of the present study was to investigate how active vitamin D, 1,25(OH)2D3, affects beta cells directly by establishing its effects on global gene expression in healthy murine islets.

Extraskeletal effects of vitamin D.

The presence of vitamin D receptors in diverse tissues like immune cells, beta-cells in the pancreas, and cardiac myocytes has prompted research to evaluate the impact of vitamin D deficiency on the occurrence of immune diseases, diabetes, and cardiovascular disease (CVD). The expression of receptors not only in normal cells, but also in cancer cells including breast, prostate, and colon cancer cells has moreover opened the path to therapeutic exploitation of vitamin D or its metabolites and hypocalcemic structural analogues as pharmaceutical tools in the fight against chronic non-communicable diseases like diabetes, CVD, and cancer.

Vitamin D and diabetes: its importance for beta cell and immune function.

Experimental evidence indicates that vitamin D may play a role in the defense against type 1 diabetes (T1D) as well as type 2 diabetes (T2D). Epidemiological data have established a link between vitamin D deficiency and an increased incidence of both T1D and T2D, whereas early and long-term vitamin D supplementation may decrease the risk of these disorders. The protective effects of vitamin D are mediated through the regulation of several components such as the immune system and calcium homeostasis.