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Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor
Author(s) -
Zeitz Ute,
Weber Karin,
Soegiarto Desi W.,
Wolf Eckhard,
Balling Rudi,
Erben Reinhold G.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0424fje
Subject(s) - calcitriol receptor , endocrinology , medicine , pancreas , glucose homeostasis , biology , islet , pancreatic islets , enteroendocrine cell , insulin , vitamin d and neurology , endocrine system , hormone , insulin resistance
It was the aim of this study to further explore the functional role of vitamin D in the endocrine pancreas. By gene targeting, we have recently generated mice in which a lacZ reporter gene is driven by the endogenous vitamin D receptor (VDR) promoter. These mice express a functionally inactive mutant VDR. Pancreatic islets but not exocrine pancreas cells showed strong lacZ reporter gene expression in mutant mice. To rule out possible influences of hypocalcemia on pancreatic endocrine function, a rescue diet enriched with calcium, phosphorus, and lactose was fed to wild‐type (WT) and VDR mutant mice. The rescue diet normalized body weight and mineral homeostasis in VDR mutants. In glucose tolerance tests, baseline blood glucose levels were unchanged in fasting VDR mutants. However, blood glucose was elevated after oral or subcutaneous glucose loading, and maximum serum insulin levels were reduced by ~60% in VDR mutants vs. WT mice on either diet. In addition, insulin mRNA levels were decreased in VDR mutant mice on both diets, whereas pancreatic β cell mass, islet architecture, and islet neogenesis were normal. These findings clearly establish a molecular role of the VDR in pancreatic insulin synthesis and secretion in vivo.