1,25-Dihydroxyvitamin D3 and pancreatic β-cell function: Vitamin D receptors, gene expression, and insulin secretion

Sooja Lee, Samuel A. Clark, Rajbir K. Gill, Sylvia Christakos

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184 Scopus citations


Previous studies have indicated that the pancreas has receptors specific for 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and that 1,25-(OH)2D3 increases insulin secretion in vitamin D-deficient rats. In this study we report that in vitamin D-replete, but calcium-deficient, rats in which 1,25- (OH)2D3 levels are elevated, insulin secretion is not altered. In addition, in in vitro studies 1,25-(OH)2D3 at concentrations of 10-10-10-7 M was consistently found to inhibit insulin secretion from islets of vitamin D- replete rats or from the rat insulinoma β-cell line RIN 1046-38. The RIN cell line was found to contain both vitamin D receptors and calbindin-D(28k) (CaBP-D(28k)) protein and mRNA. In RIN cells, treatment with sodium butyrate (2 mM for 3 days) induces a more islet phenotype, as indicated by increased insulin content and secretion and increased insulin gene expression. 1,25- (OH)2D3 treatment (50-100 nM for 48 or 72 h) had no effect on the enhanced levels of insulin secreted in the presence of butyrate. However, 2 mM sodium butyrate induced CaBP-D(28k) protein (4-fold; control, 0.8 ± 0.2; sodium butyrate, 3.5 ± 0.1 μg/mg protein) and mRNA (3-fold) in the RIN cell line, in accord with the induction by butyrate of insulin content and secretion and β-cell differentiation, suggesting a possible role for CaBP-D(28k) in these processes. Although 1,25-(OH)2D3, unlike butyrate, did not enhance insulin secretion, both 1,25-(OH)2D3 (100 nM) and butyrate (2 mM) inhibited RIN cell growth (to 69% and 28% of the control, respectively), and butyrate and 1,25-(OH)2D3 in combination led to a further inhibition of cell growth (to 13% of the control). In response to 1,25-(OH)2D3 (10 nM for 72 h), vitamin D receptors were up-regulated 313% in RIN cells [control, 37 ± 2; 1,25- (OH)2D3 treated, 115 ± 5 fmol/mg protein]. In conclusion, 1) contrary to previous studies in the vitamin D-deficient rat, our findings indicate that 1,25-(OH)2D3 action does not necessarily result in enhanced insulin secretion; 2) inhibition of cell growth and up-regulation of vitamin D receptors by 1,25-(OH)2D3 suggest that parameters in addition to insulin secretion can be affected by 1,25-(OH)2D3 in the β-cell; 3) the RIN β- cell line provides a novel in vitro system for studying the effect of the vitamin D endocrine system on pancreatic islet physiology.

Original languageEnglish (US)
Pages (from-to)1602-1610
Number of pages9
Issue number4
StatePublished - Apr 1994

All Science Journal Classification (ASJC) codes

  • Endocrinology


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