Utilized as therapeutic agents to treat type 2 diabetes, these thiazolidinediones may act to improve insulin sensitivity via induction of PPARγ in diverse tissue types, proliferation of smaller adipocytes that are more insulin-sensitive, or via mediation of the tumor necrosis factor alpha (TNF-α), leptin, or fatty acid signaling pathways [reviewed in (66)]. This evidence concerns the gene INS and type 2 diabetes mellitus.