In the context of type 2 diabetes and pathogenesis of insulin resistance, P2X7 activation behaves like a double-edged sword, which may have beneficial effects on glucose homeostasis and pancreatic islet function (71), while in conditions of overnutrition (77, 78) and exposure to obesogenic environments (79), a sustained P2X7 activation concurs to weight gain, hyperglycemia, AT inflammation, and excess of circulating free fatty acids (FFAs). This evidence concerns the gene P2RX7 and overnutrition.