M1-type macrophage-derived extracellular vesicles (M1-EVs) play a critical role in chronic low-grade tissue inflammation-induced insulin resistance, where their cargo miRNAs (such as miR-212-5p, miR-155, and miR-29a) target specific genes or modulate signaling pathways, limiting insulin secretion, impairing insulin’s suppression of glucose, potentially contributing to pancreatic β-cell failure, and obesity-induced insulin resistance (40–42). The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.