The Molecular Mechanisms by Which Vitamin D Prevents Insulin Resistance and Associated Disorders

Abstract

Numerous studies have shown that vitamin D deficiency is very common in modern societies and is perceived as an important risk factor in the development of insulin resistance and related diseases such as obesity and type 2 diabetes (T2DM). While it is generally accepted that vitamin D is a regulator of bone homeostasis, its ability to counteract insulin resistance is subject to debate. The goal of this communication is to review the molecular mechanism by which vitamin D reduces insulin resistance and related complications. The university library, PUBMED, and Google Scholar were searched to find relevant studies to be summarized in this review article. Insulin resistance is accompanied by chronic hyperglycaemia and inflammation. Recent studies have shown that vitamin D exhibits indirect antioxidative properties and participates in the maintenance of normal resting ROS level. Appealingly, vitamin D reduces inflammation and regulates Ca2+ level in many cell types. Therefore, the beneficial actions of vitamin D include diminished insulin resistance which is observed as an improvement of glucose and lipid metabolism in insulin-sensitive tissues.

Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?

“…The VDRE sequence is highly variable. The role of this complex is remodeling of chromatin and communication with RNA polymerase II to the transcription start site [ 22 , 23 , 27 , 41 , 43 ].…”

“…Recent findings reveal that the molecular mechanism of vitamin D involves insulin secretion and signaling, and thereby supports glycemic control and insulin sensitivity [ 21 ]. In light of the complex functions of vitamin D, covering the regulation of gene expression engaged in proliferation, differentiation, autophagy, apoptosis, epithelial–mesenchymal transition (EMT), modulation of cell–microenvironment interactions, antioxidants, enzymes, angiogenesis, and inflammation, it is suggested that vitamin D deficiency may be a key player of T2DM-cancer association, since it contributes to the exacerbation of disorders accompanying diabetes [ 21 , 22 , 23 , 24 , 25 , 26 ].…”

Efficacy of Dietary and Supplementation Interventions for Individuals with Type 2 Diabetes

“…Currently a consensus on the optimal vitamin D concentration or supplementation for deficiency does not exist [258,259]. The Scandinavian Nutrition Societies, the European Society for clinical and Economic Aspect of Osteoporosis and Osteoarthritis, the North American Institute of Medicine, the German Osteology governing body (DVO) and D-A-CH nutrition societies have agreed that a circulating level of 25(OH)D should not be lower than 50 nmol/L, and below 25-30 nmol/L indicates deficiency [246,260,261].…”

“…Studies investigating the efficacy of vitamin D supplementation have demonstrated significant effects on circulating vitamin D, total cholesterol, glycated hemoglobin (HbA1c), low density lipoproteins (LDL), homeostatic model assessment (HOMA-IR), and triglyceride levels, all leading to improving metabolic pathways and insulin resistance [246,262]. It is suggested that vitamin D supplementation in individuals with T2D may need to be significantly higher to achieve an adequate 25(OH)D levels due to the increased amount of adipose tissue and lower base vitamin D levels [258,263].…”

“…The active form of vitamin D can regulate the inflammatory response by inhibiting production of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β and interleukin-6) and upregulates anti-inflammatory cytokines (interleukin-6) [ 245 , 246 ]. Inflammation in conjunction with prolonged hyperglycemia leads to over production of reactive oxygen species within the body, causing oxidative stress and microvascular and macrovascular complications [ 247 ].…”