The role of vitamin D^sub 3^ in the regulation of mineral metabolism in experimental type 1 diabetes

Experimental streptozotocin type 1 diabetes in mice is characterized by a significant deficiency of vitamin D^sub 3^, detected by decreased level of serum 25(OH)D^sub 3^. This vitamin D^sub 3^ deficiency correlated with impairments of mineral metabolism in bone tissue, indicating the development of secondary osteoporosis. There was a decrease of the mass, length, and diameter (diaphysis, proximal metaphysis) in tibia of diabetic animals as compared to control. Hypocalcemia and hypophosphatemia, as well as increased levels of alkaline phosphatase activity and its isoenzymes were detected in serum of diabetic mice. In the liver of diabetic animals there was an altered expression of isoforms of vitamin D^sub 3^ 25-hydroxylase, CYP27A1 and CYP2R1, which are the major enzymes responsible for cholecalciferol biotransformation into 25(OH)D^sub 3^, the immediate precursor of hormonally active form of vitamin D^sub 3^. Administration of vitamin D^sub 3^ normalized the serum level of 25(OH)D^sub 3^; this was accompanied by a significant improvement of the state of mineral metabolism compared to the untreated group of diabetic animals. Normalization of the total and ultrafiltration calcium, as well as inorganic phosphate concentration, a decrease in serum alkaline phosphatase activity and the increase in mass, length, and diameter (diaphysis, proximal epimetaphysis) of tibia in diabetic animals treated with cholecalciferol indicated a decrease in bone resorption process. Treatment of diabetic mice with cholecalciferol had a positive effect on expression of hepatic isoforms of vitamin D^sub 3^ 25-hydroxylase (CYP27A1 and CYP2R1). Thus, impairments of mineral metabolism seen in mice with experimental diabetes mellitus are mainly determined by a deficiency of vitamin D^sub 3^ and its hormonally active forms.