Oral administration of 1,25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus

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Abstract

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the biologically active form of vitamin D, is widely recognized as a modulator of the immune system as well as a regulator of mineral metabolism. The objective of this study was to determine the effects of vitamin D status and treatment with 1,25(OH)2D3 on diabetes onset in non-obese diabetic (NOD) mice, a murine model of human type I diabetes. We have found that vitamin D-deficiency increases the incidence of diabetes in female mice from 46% (n=13) to 88% (n=8) and from 0% (n=10) to 44% (n=9) in male mice as of 200 days of age when compared to vitamin D-sufficient animals. Addition of 50 ng of 1,25(OH)2D3/day to the diet prevented disease onset as of 200 days and caused a significant rise in serum calcium levels, regardless of gender or vitamin D status. Our results indicate that vitamin D status is a determining factor of disease susceptibility and oral administration of 1,25(OH)2D3 prevents diabetes onset in NOD mice through 200 days of age.

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Animal production and maintenance

A NOD/LtJ mouse colony was produced from breeding pairs purchased from The Jackson Laboratory (Bar Harbor, ME). The animals were maintained in our facility in temperature- (70–72 °F) and humidity (40–50%)-controlled rooms under a 12-h light, 12-h dark cycle. The mice were housed in plastic cages lined with wooden shavings and consumed distilled water ad libitum. All experimental protocols were approved by the University of Wisconsin-Madison Research Animal Resources Center Committee Review Board.

Vitamin D-deficiency increases diabetes incidence and age of onset in NOD mice

To examine the effect of vitamin D status on diabetes in the NOD mouse, we examined the incidence of disease and age of onset in both vitamin D-sufficient and -deficient mice. As shown in Fig. 1, vitamin D-deficient animals (−D) exhibit a higher incidence of diabetes at 200 days of age than mice maintained in a vitamin D-sufficient (+D) state. Specifically, 88% (7/8) of vitamin D-deficient female mice were diabetic at 200 days of age, while only 46% (6/13) of vitamin D-sufficient female mice

Discussion

In the present study, we have demonstrated that a vitamin D-sufficient status alone confers partial protection against the development of diabetes in the NOD mouse. Vitamin D-deficiency resulted in an earlier mean day of onset and greater overall incidence of IDDM in both male and female mice when compared to vitamin D-sufficient animals. These results support the observations in humans that vitamin D status may be an environmental factor in determining IDDM risk. Similar to other autoimmune

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This work was supported by funds from the Wisconsin Alumni Research Foundation.

1

Present address: Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320, USA.

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