VITAMIN D DEFICIENCY AS A RISK FACTOR FOR INSULIN RESISTANCE

Abstract

Vitamin D deficiency is a global public health concern affecting more than one billion people worldwide and has been increasingly linked to impaired insulin sensitivity and the development of type 2 diabetes mellitus (T2DM). Vitamin D exerts its metabolic actions primarily through the vitamin D receptor (VDR), which is widely expressed in pancreatic β-cells, skeletal muscle, hepatocytes, and adipocytes the principal tissues governing insulin secretion and peripheral glucose uptake. The mechanisms through which vitamin D deficiency promotes insulin resistance are multifaceted and include: impairment of β-cell function and insulin gene transcription through reduced VDR-mediated signalling; dysregulation of intracellular calcium homeostasis, which disrupts the calcium-dependent activation of insulin receptor substrate-1 (IRS-1) and downstream PI3K/Akt signalling in skeletal muscle; augmentation of systemic inflammation through upregulation of nuclear factor kappa-B and increased production of pro-inflammatory cytokines including TNF-α and interleukin-6, which impair insulin signalling via serine phosphorylation of IRS-1; and transcriptional downregulation of GLUT-4 expression in muscle and adipose tissue, reducing insulin-stimulated glucose uptake.