Effect of vitamin D₃in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

Abstract

Diabetes mellitus is a growing health problem worldwide and is associated with severe liver complications. The aim of the present study is to analyse the status of metabolic and free-radical-scavenging enzymes and second messengers in the liver of streptozotocin (STZ)-induced diabetic rats, and to determine the hepatoprotective role of vitamin D 3 . All studies were performed using the liver of adult male Wistar rats. Gene expression studies were carried out using real-time PCR with specific probes. Second messenger levels were determined using 3 H-labelled Biotrak assay kits, and glucose uptake assay with D-[ 14 C]glucose. The present results show that there was a decrease in hepatic glucose uptake, malate dehydrogenase activity, glycogen content, inositol triphosphate (IP 3 ) and cyclic GMP levels, and superoxide dismutase, glutathione peroxidase, phospholipase C, cyclic AMP-responsive element-binding protein, vitamin D receptor (VDR) and insulin receptor (INSR) gene expression in the diabetic rats when compared with the controls (all P,0·05), while cyclic AMP levels and GLUT2 expression were increased (P,0·05). Treatment of the diabetic rats with vitamin D 3 and insulin reversed the altered parameters to near control values. In conclusion, the data suggest a novel role of vitamin D 3 in restoring impaired liver metabolism in STZ-induced diabetic rats by regulating glucose uptake, storage and metabolism. We demonstrated that the restoring effect of vitamin D 3 is mediated through VDR modulation, thereby improving signal transduction and controlling free radicals in the liver of diabetic rats. These data suggest a potential role for vitamin D 3 in the treatment of diabetes-associated hepatic complications.Key words: Vitamin D: Diabetes: Liver: Oxidative stress: Metabolism: Insulin Diabetes-associated complications are major causes of morbidity and mortality. The liver plays a unique role in glucose homeostasis. Because of its anatomical location, it is ideally suited to control the systemic supply of absorbed nutrients, and it is one of only two organs that both consume and produce substantial amounts of glucose. The central role of the liver in the maintenance of blood glucose levels is assured by complex regulation by metabolic substrates, insulin and other hormones (1) . Diabetes-associated hyperglycaemia and hypoinsulinaemia lead to the impairment of hepatic glucose and lipid metabolism. Virtually, the entire spectrum of liver diseases is seen in patients with diabetes, including liver cirrhosis, a significant cause of death in diabetic patients, even more relevant than CVD (2) . Interest in the development of novel antidiabetic agents has been fuelled by the intense complications due to therapeutic treatment of diabetes and associated liver failure (2,3) . An increased prevalence of diabetes has been observed in vitamin D-deficient individuals (4) , and our previous study has shown that vitamin D 3 treatment restores blood glucose homeostasis in streptozotocin (STZ)-induced diabetic rats (5) . Bind...

Evaluation of 25(OH) Vitamin D 3 with Reference to Magnesium Status and Insulin Resistance in T2DM

“…Our results are consistent with previous reports that depicted the fact that hypovitaminosis D in adults may influence the risk of developing diabetes and metabolic syndrome [18,19]. A previous study has shown that Vitamin D levels are positively correlated with insulin sensitivity and negatively correlated with HbA1c levels, indicating Vitamin D deficiency as a predisposing factor in the pathogenesis of diabetes mellitus and cardiovascular diseases [20].…”

“…Proper mechanisms linking hypovitaminosis D with increased blood glucose level remains unclear, but there are some supporting studies which indicate that Vitamin D may directly affect pancreatic β-cell secretory functions through nuclear Vitamin D receptors and may affect the insulin sensitivity through insulin receptor expression regulation of intracellular receptors [10][11][12]. In a few animal studies, administration of calcitriol (activated form of Vitamin D) has been shown to prolong the onset of Type 1 Diabetes mellitus, mainly through immune regulation [19,31]. This is mainly because of effect of Vitamin D on inflammatory pathway [4,19].…”

“…In a few animal studies, administration of calcitriol (activated form of Vitamin D) has been shown to prolong the onset of Type 1 Diabetes mellitus, mainly through immune regulation [19,31]. This is mainly because of effect of Vitamin D on inflammatory pathway [4,19].…”

Efecto del ergocalciferol (vitamina D2) y el colecalciferol (vitamina D3) sobre el control de la glicemia en ratas

“…La administración de vitamina D 2 y D 3 mostró niveles de glicemia significativamente menores en todos los grupos de experimentación en comparación al control positivo, concordando con los estudios realizados por George et al (15) , quienes demostraron que el tratamiento con vitamina D 3 restauró significativamente la homeostasis de la glucosa en la sangre en ratas diabéticas inducidas por estreptozotocina (STZ). Asimismo, Elseweidy et al (12) , en un estudio con un modelo de inducción de diabetes similar al nuestro, obtuvieron diferencias significativas en comparación a su grupo control positivo usando dosis de 170 UI/semana de vitamina D 3 .…”

Curcumin pretreatment mediates antidiabetogenesis via functional regulation of adrenergic receptor subtypes in the pancreas of multiple low-dose streptozotocin-induced diabetic rats

“…At the end of incubation, antibody bound and free insulin were separated by the second antibody-polyethylene glycol aided separation method. Radioactivity associated with the bound fraction of sample and standards was measured to quantitate insulin concentration of samples [19].…”