Effect of vitamin D supplementation on CREB-TrkB-BDNF pathway in the hippocampus of diabetic rats.

OBJECTIVES: Cyclic AMP (adenosine monophosphate) response element-binding protein (CREB) and Brain-derived neurotrophic factor (BDNF) are reported to broadly involve in learning capacity and memory. BDNF exerts its functions via tropomyosin receptor kinase B (TrkB). BDNF transcription is regulated by stimulating CREB phosphorylation. The CREB-TrkB-BDNF pathway is reported to be affected by diabetes, which may contribute to its cognitive deficits. This study was conducted to investigate the effect of vitamin D supplementation on the hippocampal fraction of this pathway in an animal model of type-1 diabetes mellitus (T1DM). MATERIALS AND METHODS: Thirty-six adult male Sprague-Dawley rats were randomly divided into 4 groups as follows: Group 1: normal healthy rats (n=8); group 2: normal healthy rats receiving sesame oil supplementation as placebo (n=8); Group 3: diabetic rats receiving sesame oil (n=10); and Group 4: diabetic rats treated with 4300 IU/kg/week vitamin D dissolved in sesame oil (n=10). Diabetes was induced by intraperitoneal (IP) injection of streptozotocin. Blood and hippocampal samples were acquired at the end of the experiment. RNA was extracted from the hippocampus, and real-time PCR (polymerase chain reaction) was performed for BDNF and TrkB gene expression. RESULTS: Administration of vitamin D (4300 IU/kg/week) in a T1DM animal model increased CREB phosphorylation in the hippocampus, but the serum and hippocampal BDNF levels and TrkB and BDNF gene expression did not change significantly. CONCLUSION: Vitamin D increased hippocampal CREB phosphorylation in a T1DM animal model. Our findings showed that vitamin D might be protective against central nervous system complications in diabetes. However, future studies are warranted.

Vitamin D suppresses cellular pathways of diabetes complication in liver.

OBJECTIVES: The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into three groups (8 rats in each group). The first group served as control and the other two groups received an intraperitoneal injection of 45 mg/kg streptozotocin to develop diabetes. Groups were treated for four weeks either with placebo or vitamin D (two injections of 20000 IU/kg). Thereafter, serum levels of glucose, insulin and HbA1c were assessed. Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT). RESULTS: Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005). Insulin level increased as a result of vitamin D treatment compared to control (3.31±0.65 vs. 2.15±0.79; P= 0.01). Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake. Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively). CONCLUSION: Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.

The Effect of Vitamin D Supplementation on Serum and Muscle Irisin Levels, and FNDC5 Expression in Diabetic Rats.

BACKGROUND: Diabetes mellitus and metabolic disorders are a major burden on the healthcare system. Irisin is a novel myokine reported to have beneficial effects on glucose and lipid metabolism. Vitamin D deficiency has been implicated in the development of diabetes and hold a critical role in diabetes-related complications. In the present study, we examined the efficacy of vitamin D supplementation on serum irisin levels, skeletal muscle irisin levels, and the expression of the irisin precursor, FNDC5 (fibronectin-type III domain-containing 5) in type I diabetes mellitus rats. METHODS: Thirty-six adult male Sprague-Dawley rats (150 - 250 g) were randomly divided into four groups: group I: healthy control rats with no treatment (n=8), group II: healthy control rats receiving sesame oil as a placebo (n=8), group III: diabetic rats receiving sesame oil as placebo (n=10), group IV: diabetic rats treated with 4300 IU/kg/week vitamin D (n=10). Diabetes was induced by intraperitoneal (IP) injection of streptozotocin. At the end of the vitamin D intervention blood and triceps muscle samples were collected. RNA was extracted from muscle and real-time PCR was performed to examine FNDC5 gene expression. RESULTS: Our study showed that the administration of vitamin D (4300 IU/kg/week) in a streptozotocin-diabetic rat model resulted in increased serum vitamin D levels, FNDC5 gene expression and muscle irisin levels. However, the levels of serum irisin were not significantly changed by the administration of vitamin D. CONCLUSION: In conclusion, we show that vitamin D supplementation enhances serum vitamin D levels, FDNC5 gene expression and muscle irisin levels in the streptozotocin-diabetic rat model. Our study highlights the potential therapeutic effect of vitamin D supplementation for diabetes mellitus.

Vitamin D and diabetic nephropathy: A systematic review and meta-analysis.

OBJECTIVE: There has been a long history documenting the use of different vitamin D derivatives as therapy for renal diseases. However, to our knowledge, there is no comprehensive assessment of the relation between vitamin D deficiency and risk for diabetic nephropathy (DN). Additionally, the effect of vitamin D supplementation on DN is still unclear. The aim of this meta-analysis was to assess these issues by pooling together the results from cross-sectional studies and clinical trials. METHODS: A systematic literature search of PubMed, Scopus, and Google Scholar was conducted, ending in September 2014. For cross-sectional studies, odds ratio was used as a measure of the association between vitamin D status and risk for DN; for clinical trials, mean and SD of the main outcome (urine albumin-to-creatinine ratio [UACR]) in intervention and placebo groups were considered for analysis. RESULTS: The final selected articles were published between 2009 and 2014. In all, 3700 and 219 patients were enrolled in observational and interventional studies, respectively. The pooled odds ratio from six cross-sectional studies was 1.80 (95% confidence interval [CI], 1.25-2.59; P = 0.002), indicating a significant inverse association between serum vitamin D status and risk for nephropathy in patients with diabetes. However, the pooled data of UACR levels in clinical trials suggested no significant change following vitamin D supplementation (17.98; 95% CI, -35.35 to 71.32; P = 0.51). CONCLUSION: This meta-analysis showed the higher risk for nephropathy in vitamin D-deficient patients with diabetes. Pooling the results of available clinical trials after vitamin D supplementation did not support causality in this association.

Association of vegan diet with RMR, body composition and oxidative stress.

BACKGROUND: There is increasing evidence to suggest that a vegetarian diet low in fat and high in complex carbohydrates offers the potential for decreasing the risk of chronic disease. However, there is little information about the effect of vegetarian diets on resting metabolic rate (RMR). The objective of this study was to determine the association of vegan diet with RMR and body composition and oxidative stress. MATERIAL AND METHODOLOGY: This research is a cross-sectional descriptive analytic study in which two groups of vegetarians and non vegetarians were compared. RMR was determined by indirect calorimetry, the amount of body fat mass (FM), the percentage of free fat mass (FFM), the markers of oxidative stress (MAD), poteins (PCO) and total anti-oxidatant capacity were measured in 20 vegetarians and 20 non-vegetarians. The two groups were matched with regard to body mass index, sex and menstrual cycle. Energy and macronutrient intakes were determined using a 3-day food record and body composition was determined by bioelectric impedance. RESULTS: VEG reported a lower relative intake of protein (40.45 ± 19.41 g, 56.96 ± 11.94 g, p = 0.04), whereas no differences were observed in daily energy, carbohydrate or fat intakes and body composition. NVEG exhibited a higher absolute RMR (1354.7 ± 192.6, 1569.10 ± 348.24 Kcal/24 h, p = 0.02). PCO plasma density was seen significantly higher among non-vegetarians (1.09 ± 3.6, 0.81 ± 0.42, p = 0.02). No significant differences were seen in plasma density of TAC between two groups and MAD was higher amoung vegetarians. CONCLUSION: These results suggest that the lower RMR observed in VEG is partially mediated by differences in dietary macronutrient composition.