Diabetes was shown to be associated with a considerable lowering of 25(OH)D3 in blood serum of mice. Vitamin D3 deficiency was correlated with impaired mineral metabolism in bone tissue, indicating the development of secondary osteoporosis. A decrease in weight, length and diameter (diaphysis, proximal metaepiphysis) of tibia in diabetic animals was observed as compared with control. Diabetes caused hypocalcemia, hypophosphatemia and increased enzymatic activity of alkaline phosphatase (ALP) and its isoenzymes in serum. This changes were accompanied by the impairments of vitamin D3 25-hydroxylase isoforms (CYP27A1 and CYP2R1) expression, which are the main enzymes of cholecalciferol biotransformation to 25(OH)D3 - precursor of hormonally active form of vitamin D3. A decrease in bone resorption processes was established after vitamin D3 administration as it is evident from normalization of bone morphometrical parameters and mineral metabolism in diabetic mice. Vitamin D3 ability to counter diabetes-induced alterations in bone tissue can be ascribed, at least in part, to its positive effects on the formation of vitamin D3 hormonally active forms.
Pri éksperimental'nom streptozototsinovom diabete 1 tipa u mysheĭ voznikaet znachitel'nyĭ defitsit vitamina D3, detektiruemyĭ po snizheniiu urovnia 25(OH)D3 v syvorotke krovi. Nedostatochnost' vitamina D3 korrelirovala s narusheniiami mineral'nogo obmena v kostnoĭ tkani, chto svidetel'stvuet o razvitii vtorichnogo osteoporoza. Nabliudalos' umen'shenie massy, dliny i diametra (diafiza, proksimal'nogo metaépifiza) bol'shoĭ bertsovoĭ kosti u zhivotnykh s diabetom po sravneniiu s kontrol'nymi. V syvorotke krovi pri diabete byla obnaruzhena vyrazhennaia gipokal'tsiemiia i gipofosfatemiia, a takzhe povyshenie fermentativnoĭ aktivnosti shchelochnoĭ fosfatazy i ee izofermentov. Prodemonstrirovano narushenie ékspressii izoform vitamin D3 25-gidroksilazy pecheni CYP27A1 i CYP2R1, kotorye iavliaiutsia osnovnymi fermentami biotransformatsii kholekal'tsiferola v 25(OH)D3 – predshestvennika gormonal'no aktivnykh form vitamina D3. Vvedenie vitamina D3 obuslavlivalo normalizatsiiu urovnia 25(OH)D3 v syvorotke krovi, chto soprovozhdalos' znachitel'nym uluchsheniem sostoianiia mineral'nogo obmena po sravneniiu s gruppoĭ diabeta. Normalizatsiia kontsentratsii obshchego, ul'trafil'tratsionnogo kal'tsiia i neorganicheskogo fosfata, umen'shenie aktivnosti shchelochnoĭ fosfatazy v syvorotke krovi, a takzhe uvelichenie massy, dliny, diametra (diafiza, proksimal'nogo épimetafiza) bol'shoĭ bertsovoĭ kosti u diabeticheskikh zhivotnykh, kotorym vvodili kholekal'tsiferol, svidetel'stvovali o umen'shenii protsessov kostnoĭ rezorbtsii. Takzhe byli otmecheny polozhitel'nye izmeneniia ékspressii izoform vitamin D3 25-gidroksilazy pecheni (CYP27A1 i CYP2R1). Takim obrazom, narusheniia mineral'nogo obmena pri éksperimental'nom sakharnom diabete u mysheĭ opredeliaiutsia defitsitom vitamina D3 i ego gormonal'no aktivnykh form.
Keywords: CYP27A1; CYP2R1; bone resorption markers; diabetes; secondary osteoporosis; vitamin D3.