INS and type 2 diabetes mellitus: Synthetic PPARγ agonists, such as thiazolidinediones (TZDs), which were first reported as insulin-sensitizing drugs in the early 1980s (47), and have been widely used as a therapeutic compound in the treatment of type 2 diabetes, but their underlying mechanism remain unclear until the middle 1990s, when scientists found TDZs were ligands for PPARγ (48).TZDs-induced activation of PPARγ regulates the production and secretion of adipokines, including adiponectin, leptin, and resistin, which impact insulin sensitivity through endocrine signaling pathways (49–51).