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Growing evidence suggests that vitamin D3 (D3, cholecalciferol) deficiency and impaired signaling of the hormonally active form of D3, 1α,25(OH)2D3 (1,25D3), through its cellular receptor (VDR) can be significant risk factors for the development of numerous multifactorial diseases, including diabetes. Our investigation was aimed at researching the D3 status in relation to the state of the D3 auto-/paracrine system in the brain and clarifying the effectiveness of the therapeutic use of D3 as a neuroprotective agent in experimental type 2 diabetes mellitus (T2DM). T2DM was induced in male Wistar rats by a combination of a high fat diet and a low dose of streptozotocin (25 mg/kg BW). Diabetic animals were treated with or without cholecalciferol (1,000 IU/kg BW, 30 days). The content of 25-hydroxyvitamin D3 (25D3) in blood serum and brain tissue was determined by ELISA. Analysis of mRNA expression of CYP24A1 and CYP27B1 genes was performed by RT-PCR. Protein levels of VDR, vitamin D3 binding protein (VDBP), CYP27B1 and CYP24A1 were investigated by Western blotting. A significant T2DM-associated decrease in the content of 25D3 in the blood serum was revealed, which correlated with a reduced content of this metabolite in the brain tissue. Impaired D3 status in animals with T2DM was accompanied by an increase in the levels of mRNA and protein of both 25D3 lα-hydroxylase (CYP27B1) and 1,25-hydroxyvitamin D3-24-hydroxylase (CYP24A1), which, respectively, provide local formation and degradation in the nervous tissue of the hormonally active form of D3 – 1,25D3. At the same time, a significant T2DM-induced down-regulation of the brain content of VDBP was shown. In addition, diabetes caused a slight increase in the protein expression of the VDR, through which the auto-/paracrine effects of 1,25D3 are realized in the brain. We have established a complete or partial corrective effect of cholecalciferol on D3 status, its bioavailability in the CNS and the level of protein expression of CYP27B1 and CYP24A1 in the brain of rats with T2DM. Abnormal D3 status in animals with T2DM was accompanied by compensatory changes in the expression of key components of the auto-/paracrine vitamin D3 system. Cholecalciferol was demonstrated to be partially effective in counteracting the impairments caused by T2DM. Keywords: 25-hydroxyvitamin D3, brain, type 2 diabetes, vitamin D3, vitamin D3 auto-/paracrine system
Growing evidence suggests that vitamin D3 (D3, cholecalciferol) deficiency and impaired signaling of the hormonally active form of D3, 1α,25(OH)2D3 (1,25D3), through its cellular receptor (VDR) can be significant risk factors for the development of numerous multifactorial diseases, including diabetes. Our investigation was aimed at researching the D3 status in relation to the state of the D3 auto-/paracrine system in the brain and clarifying the effectiveness of the therapeutic use of D3 as a neuroprotective agent in experimental type 2 diabetes mellitus (T2DM). T2DM was induced in male Wistar rats by a combination of a high fat diet and a low dose of streptozotocin (25 mg/kg BW). Diabetic animals were treated with or without cholecalciferol (1,000 IU/kg BW, 30 days). The content of 25-hydroxyvitamin D3 (25D3) in blood serum and brain tissue was determined by ELISA. Analysis of mRNA expression of CYP24A1 and CYP27B1 genes was performed by RT-PCR. Protein levels of VDR, vitamin D3 binding protein (VDBP), CYP27B1 and CYP24A1 were investigated by Western blotting. A significant T2DM-associated decrease in the content of 25D3 in the blood serum was revealed, which correlated with a reduced content of this metabolite in the brain tissue. Impaired D3 status in animals with T2DM was accompanied by an increase in the levels of mRNA and protein of both 25D3 lα-hydroxylase (CYP27B1) and 1,25-hydroxyvitamin D3-24-hydroxylase (CYP24A1), which, respectively, provide local formation and degradation in the nervous tissue of the hormonally active form of D3 – 1,25D3. At the same time, a significant T2DM-induced down-regulation of the brain content of VDBP was shown. In addition, diabetes caused a slight increase in the protein expression of the VDR, through which the auto-/paracrine effects of 1,25D3 are realized in the brain. We have established a complete or partial corrective effect of cholecalciferol on D3 status, its bioavailability in the CNS and the level of protein expression of CYP27B1 and CYP24A1 in the brain of rats with T2DM. Abnormal D3 status in animals with T2DM was accompanied by compensatory changes in the expression of key components of the auto-/paracrine vitamin D3 system. Cholecalciferol was demonstrated to be partially effective in counteracting the impairments caused by T2DM. Keywords: 25-hydroxyvitamin D3, brain, type 2 diabetes, vitamin D3, vitamin D3 auto-/paracrine system
Background. There is currently a debate about the diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescent girls. The role of vitamin D in the pathogenesis of PCOS remains unclear. The purpose: to study the serum level of 25(OH)D in adolescent girls and to analyze its connection with PCOS. Materials and methods. Twenty-three patients aged 14–18 years with PCOS were examined on the basis of the Chernivtsi Regional Clinical Hospital. The control group consisted of 25 girls of a similar age without disorders of gynecological status. Body mass index, degree of hirsutism, hormonal, lipid profile, HOMA index, calcium concentration were determined according to generally accepted methods. Levels of serum 25(OH)D were measured using the electrochemiluminescence method. Sonography of the ovaries was performed. Statistical data were processed using the Microsoft Excel 2020 program on a personal computer and the package of application programs Statistica for Windows v. 7.0 (StatSoft Inc.). Ethical principles are observed in the work, taking into account the main provisions of the ІCH GCР and the Declaration of Helsinki. Results. The premorbid background of the examined adolescent girls included allergic reactions, infectious, respiratory, digestive, and urinary diseases. The level of 25(OH)D was inversely proportional to body mass index (r = –0.23, p < 0.05), hirsutism (r = –0.22, p < 0.05), HOMA-IR (r = –0.198, p < 0.05). Deficiency of 25(OH)D in adolescent girls with excess body weight was associated with dyslipidemia (r = –0.33, p < 0.01). Indicators of the serum level of calcium varied within the reference values. The odds ratios for the development of PCOS in adolescent girls were: 25(OH)D [2.35, 95% CI: 1.84–5.06, p < 0.05]; excess body weight [2.09, 95% CI: 1.94–4.56, p < 0.05], clinical hyperandrogenism (hirsutism) [2.98, 95% CI: 2.12–4.19, р < 0.01]; HOMA-IR [2.30, 95% CI: 1.02–5.15, р = 0.04]; high-density lipoproteins [2.56, 95% CI: 1.92–5.87]. Conclusions. PCOS occurs on the background of 25(OH)D insufficiency or deficiency. 25(OH)D deficiency, excess body weight, clinical hyperandrogenism, HOMA-IR, and high-density lipoproteins increase the risk of PCOS in adolescent girls.
Background. Today, diabetes mellitus is an actual problem, characterized by a progressive increase in the number of patients with a high frequency of complications that require early diagnosis and timely treatment. Diabetic nephropathy is among the most common microvascular lesions. Patients may have clinical manifestations of diabetic kidney disease that go beyond the classic symptoms and have extrarenal consequences in the form of bone mineral disorders. The purpose of the work is to carry out a comprehensive assessment of early markers of kidney damage and changes in bone disorder indicators in patients with type 2 diabetes and to identify correlations between the studied parameters. Materials and methods. Eighty patients with type 2 diabetes participated in the study. They were divided according to the glomerular filtration rate: GFR < 60 ml/min/m2 (1st group, n = 26), GFR ≥ 60 ml/min/m2 (2nd group, n = 54). Results. Analysis of early markers of kidney damage revealed some significant differences between the groups. Indicators of daily urine albumin-creatinine ratio, serum cystatin C, parathyroid hormone, uric acid, and vitamin D-binding protein were significantly higher in patients with GFR < 60 ml/min/m2. The average level of vitamin D (25OH) in both groups corresponded to a deficient state, and the 1st group was marked by a statistically significantly lower level compared to the 2nd group: 12.32 ± 4.84 and 16.72 ± 5.82 ng/ml, respectively (p = 0.001). In the 1st group, vitamin D deficiency was observed in 92.3 % of cases, and in the 2nd group, in 74.1 % (p = 0.56). According to the correlation analysis, some reliable relationships were found: in the 1st group, there was a negative correlation between GFR and parathyroid hormone (r = –0.816, p < 0.001). An inverse correlation was revealed between GFR and cystatin C in the 1st (r = –0.862, p < 0.001) and 2nd groups (r = –0.322, p = 0.18). Among all examined participants, there was a linear negative correlation between GFR and uric acid (r = –0.452, p < 0.001). Vitamin D (25OH) didn’t have a significant relationship with GFR, however, we found a negative correlation with the daily urine albumin-creatinine ratio (r = –0.253, р = 0.024) and cystatin C (r = –0.303, p = 0.006), which confirms the role of cholecalciferol in mineral bone disorders in patients with chronic kidney disease. In our study, an inverse correlation was found between GFR and vitamin D-binding protein in the 1st (r = –0.436, p = 0.26) and 2nd group (r = –0.283, p = 0.038), which probably indicates a possible compensatory response of transport protein to initial mineral bone disorders in patients with diabetic kidney disease. Conclusions. Early detection of bone mineral disorders in diabetic kidney disease is important to increase the efficiency of managing patients with type 2 diabetes and timely treatment, prevention of cardiovascular complications and bone metabolism disorders
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