Vitamin D metabolism in the chronic streptozotocin-induced diabetic rat.
Alterations in circulating vitamin D3 metabolites 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 less than 0.01) decreased 1 alpha-hydroxylase activity and enhanced (P less than 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.
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002762:Cholecalciferol / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D001786:Blood Glucose; D002762:Cholecalciferol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase