الفهرس 
Introduction & Aim of The WorkOnly 14 pages are availabe for public view
 |  | from | 143 |  |  |
| | | from | 143 | | |
Abstract
=Type 2 diabetes mellitus (T2DM) represents a metabolic disorder with major global health-care problem. The World Health Organization has predicted that the global prevalence of diabetes will increase from 2.8% in 2000 to 4.4% in 2030. The main known function of Vitamin D3 is to regulate calcium, phosphorus homeostasis and bone metabolism. Vitamin D3 may influence several non-skeletal medical conditions, including cardiovascular disease, cancer, autoimmune disorders, psoriasis, multiple sclerosis, and T2DM. It has been reported that there is an inverse relationship between circulating level of Vitamin D and the prevalence of T2DM. In fact, Vitamin D deficiency has been suggested as a risk factor for T2DM. Some studies indicated that Vitamin D may play a functional role on glucose tolerance through its effects on insulin secretion and insulin sensitivity. This study aimed to assess the role of vitamin D3 supplementation to diabetic rats (T2DM), to find the exact effect on glycemic control and insulin resistance and to highlight the underlying pathophysiological mechanisms.Animals were divided into five groups:-group 1 (normal control): 10 rats kept on regular diet and received no treatment.-group 2 (normal+1000IU vitamin D3): 5 rats kept on regular diet with 1000IU vitamin D3 supplementation for 45 days. -group 3 (diabetic control): 15 rats with STZ induced diabetes mellitus and high fat diet receiving no treatment for 45 days. -group 4 (diabetic +1000IU vitamin D3): 15 rats with STZ induced diabetes mellitus, fed high fat diet, and supplemented with 1000IU vitamin D3 once daily for 45 days. -group 5 (diabetic +2000IU vitamin D3): 15 rats with STZ induced diabetes mellitus, fed high fat diet, and supplemented with 2000IU vitamin D3 once daily for 45 days. At the end of the study blood and tissue samples were collected and subjected to: 1.Biochemical analysis: FBG, insulin, and lipid profile (Total cholesterol, TAG, HDL-C, and LDL-C).2.Inflammatory markers detection: TNF-α and NF-κB p65.3.Oxidative stress and antioxidant enzymatic activity measurement: SOD, GSH and MDA.4.Molecular analysis: determination of gene expression of pancreatic (GLUT-2, INSR, VDR, and Caspase-3), hepatic (GLUT-2, INSR, and VDR), GLUT-4.5.Histopathological examination using Hematoxylin and eosin stain for pancreatic, hepatic, and muscle tissues.The most important obtained results are:●There was significant reduction of serum glucose, serum insulin and HOMA IR, total cholesterol, LDH-C, and significant increase of HDL-C in Diabetic + 1000IU Vit. D3 and Diabetic + 2000IU Vit. D3 groups when compared to diabetic group. ●In pancreatic and liver tissues, vitamin D (both doses) significantly increased GLUT-2, INSR, VDR gene expressions compared to diabetic un treated rats (p<0.05). In muscle tissue, a significant increase of gene expression of GLUT-4 was observed compared to diabetic rats. ●All results were superior in high dose compared to the low one.●Gel Electrophoresis of the PCR showed that diabetes mellitus results in increased methylation of GLUT-2 gene which is partially reversed by vitamin D3 (both doses). The same can be implied from amplified GLUT-2 gene electrophoresis of liver tissue samples.It can be concluded that through the anti-inflammatory, antioxidant and anti-apoptotic mechanisms, vitamin D3 lowers serum glucose level in rats with type 2 diabetes millets. This can be at least partially mediated by affecting the degree of GLUT-4 methylation.Low level of Vitamin D3 might play a significant role in T2DM pathogenesis, and this finding may have therapeutic implications as cautious Vitamin D3 supplementation may improve glycemic control and oxidative status in T2DM.Limitations of the study:1.The present study was on a small sample size.2.Inclusion criteria included only type II diabetes.