INS and type 2 diabetes mellitus: PTP1B is widely reported as a key regulator of metabolic signals, including insulin signaling and leptin signaling, that negatively regulate the insulin pathway through JAK2-STAT3 and CREB/lysine methyltransferase 5 A (KMT5A), which are dysfunctional in T2DM and obesity11,168,169 (Fig. 8).