Vitamin D Metabolism in the Chronic Streptozotocin-Induced Diabetic Rat*

Abstract

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.

Incidence of Vitamin D Deficiency and Its Relevance to Bone Metabolism in Japanese Postmenopausal Women with Type 2 Diabetes Mellitus

“…The present study did not provide data that can explain the higher prevalence of hypovitaminosis D in the patients with type 2 diabetes mellitus. Previous studies have indicated that the chronic insulin-deficient state leads to the reduced 1-alpha-hydroxylase activity and increased 24-hydroxylase activity in chronic streptozotocininduced diabetic rats (14). Other large prospective studies have suggested the potential beneficial effects of both vitamin D and calcium intake in reducing the risk of type 2 diabetes mellitus (15,16).…”

Hypovitaminosis D in Type 2 Diabetes Mellitus: Association with Microvascular Complications and Type of Treatment

“…Both the increase in bone turnover markers and the decrease in bone formation have been reported in diabetic populations [9,18]. It has been reported that impaired vitamin D metabolism exists in spontaneously diabetic GK rats [19], and that chronic insulin-deficiency results in a decrease in 1-α hydroxylase activity and an increase in 24-hydroxylase activity in chronic streptozotocin-induced diabetic rat [20]. The prevalence of hypovitaminosis D in the diabetic population is still controversial [9][10][11], and recent findings suggest that the lower limit of normal value of serum 25-OHD concentrations should be reevaluated [12][13][14][15][16].…”

MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

“…Employing short-term (2-week) animal models of streptozotocin diabetes, the low BMD observed in insulinopenic diabetes was earlier explained by secondary hyperparathyroidism and increased bone resorption resulting from a negative calcium balance (impaired intestinal calcium absorption; hypercalciuria) (69,70). Using more appropriate animal models of chronic diabetes (8-10 weeks), and employing time-spaced tetracycline labelled bone histomorphometry, bone formation and resorption were found to be markedly suppressed (71,72,73,74).…”