Vitamin d metabolism in the chronic streptozotocin-induced diabetic rat

Alterations in circulating vitamin D₃ metabo-lites have been documented in both experimental and human diabetes mellitus. Using a recirculating hepatic perfusion system and in vitro kidney mitochondrial assays, we studied vitamin D₃ hydroxylation in control and insulin-deficient rats 6 weeks after the induction of streptozotocin-diabetes. Vitamin D₃-25-hydroxylase activity, assessed by hepatic conversion of [³H]vitamin D₃ to [³H]25-hydroxyvitamin D₃ during a 4-h perfusion, was similar in diabetic and control animals. The hepatic degradation of 25-hydroxyvitamin D₃ to more polar metabolites was also normal, as was glucuronide conjugation and biliary excretion of vitamin D₃ metabolites. The chronic insulin-deficient state resulted in a significantly (P < 0.01) decreased 1α-hydroxylase activity and enhanced (P < 0.001) renal 24-hydroxylase activity. These alterations in vitamin D metabolism may relate to the deranged mineral homeostasis and skeletal morphology observed in rats and humans with chronic insulin deficiency.