INS and Obesity: Fundamentally, the excessive accumulation and expansion of white adipose tissue (WAT) is related to a remodeled microenvironment in obesity characterized by aberrant inflammation, fibrosis, hypoxia, dysregulated secretion of adipokines, and disrupted mitochondrial function (34, 36), which impairs insulin signaling, triggers insulin resistance, reduces insulin-stimulated glucose-transport activity (37), and speeds β-cell dysfunction, playing a pivotal role in the pathogenesis of T2DM.