Association of increased renal <i>Cyp24a1</i> gene expression with low plasma 1,25-dihydroxyvitamin D levels in rats with streptozotocin-induced diabetes

  • Tajiri Mari
    Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, University of Tokushima Graduate School
  • Nakahashi Otoki
    Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, University of Tokushima Graduate School Division of Functional Food Chemistry, Institute for Health Science, Tokushima Bunri University
  • Kagawa Tomohiro
    Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, University of Tokushima Graduate School
  • Masuda Masashi
    Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, University of Tokushima Graduate School
  • Ohminami Hirokazu
    Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, University of Tokushima Graduate School
  • Iwano Masayuki
    Department of Nephrology, Faculty of Medical Sciences, University of Fukui
  • Takeda Eiji
    Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, University of Tokushima Graduate School
  • Taketani Yutaka
    Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, University of Tokushima Graduate School
  • Yamamoto Hironori
    Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, University of Tokushima Graduate School Department of Nephrology, Faculty of Medical Sciences, University of Fukui Department of Health and Nutrition, Faculty of Human Life, Jin-ai University

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Abstract

<p>Decreases in plasma vitamin D concentrations have been reported in diabetes, although the mechanism involved in this decrease is unclear. Here, we investigated the association between Cyp24a1, a vitamin D catabolic enzyme, and abnormalities in vitamin D metabolism in streptozotocin-induced diabetes rats, an animal model of type 1 diabetes. Plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were significantly lower in streptozotocin-induced diabetes rats and renal Cyp24a1 mRNA expression levels were increased. Western blotting analysis of streptozotocin-induced diabetes rats kidney tissues with anti-CYP24A1 antibody showed a strong signal around 40 kDa, which differs from the predicted 50–55 kDa molecular weight for full-length Cyp24a1 and could represent the Cyp24a1-splicing variant that lacks exons 1 and 2. We observed high levels of renal Cyp24a1-splicing variant mRNA expression in streptozotocin-induced diabetes rats. We also confirmed transcriptional up-regulation of endogenous Cyp24a1 mRNA expression through glucocorticoid receptors by glucocorticoid in opossum kidney proximal cells. Taken together, our results indicated that high Cyp24a1 expression levels may play a role in the decrease of plasma 1,25(OH)2D levels in streptozotocin-induced diabetes rats. High plasma corticosterone levels in diabetes may affect transcriptional regulation to promote increases in Cyp24a1 expression.</p>

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