Effects of 1,25-dihydroxyvitamin D3 and the analogues MC903 and KH1060 on interleukin-1 beta-induced inhibition of rat pancreatic islet beta-cell function in vitro.
The cytokine interleukin-1 beta (IL-1 beta) has been proposed to be involved in pancreatic beta-cell destruction during the development of autoimmune insulin-dependent diabetes mellitus. It has been demonstrated that 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) inhibits T-lymphocyte and monocyte functions in vitro, probably through an effect on cytokine actions, and that in vivo treatment with vitamin D can prevent pancreatic insulitis in diabetes-prone NOD mice. In this study isolated rat pancreatic islets were exposed to human IL-1 beta (25 U/ml) in the absence or presence of 1,25-(OH)2D3 or the analogues MC903 and KH1060 for 48-72 h in tissue culture, whereupon medium insulin accumulation, islet DNA and insulin contents, glucose-stimulated insulin secretion and glucose oxidation rates were assessed. All three vitamin D derivatives counteracted the suppressive effect of IL-1 beta on medium insulin accumulation, 1,25-(OH)2D3 being active at concentrations down to 0.1 nM, i.e., 1-2 orders of magnitude more efficacious than the analogues. However, only KH1060 opposed the suppressive effect of IL-1 beta on islet glucose-stimulated insulin secretion and glucose oxidation rate despite the fact that KH1060 itself reduced the islet DNA and insulin content by approximately 10% and 30%, respectively. The protective effect observed against IL-1 beta-induced beta-cell dysfunction might be related to a beneficial action of vitamin D3 on the mitochondrial calcium metabolism of the beta-cells.
Department of Medical Cell Biology, Uppsala University, Sweden.
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Sandler
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Buschard
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Bendtzen
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley
D007328:Insulin; D007375:Interleukin-1; C074279:KH 1060; C055085:calcipotriene; D004247:DNA; D002117:Calcitriol; D005947:Glucose