Vitamin D receptors, tissue growth and insulin dependent diabetes.

Abstract

The studies described in this thesis evaluate the effect of insulin dependent diabetes on vitamin D receptors (VDR) and tissue growth in two models of insulin dependent diabetes: the streptozotocin-induced diabetic rat and the spontaneously diabetic BB rat. In both models, untreated diabetes was associated with decreased circulating 1,25-dihydroxycholecalciferol (1,25 DHCC), disturbed mineral homeostasis and up regulation of intestinal VDRs. The increase in unoccupied VDRs was associated with compensatory tissue growth in the intestine and hyperplasia. Low circulating 1,25 DHCC prevented amplification of the action of 1,25 DHCC despite up-regulation of intestinal VDRs, as evidenced by a reduction in calbindin D-9K in the diabetic intestine. The above parameters were normalized in STZ diabetic rats treated with exogenous insulin. There were no alterations in VDR numbers in kidneys or thymus of untreated diabetic animals, indicating that up-regulation of VDRs did not occur in all vitamin D target tissues. Unlike the intestine, compensatory growth in the kidney was not associated with hyperplasia, suggesting tissue specific changes in 1,25 DHCC metabolism during untreated diabetes which may be related to hyperplasia.