INS and diabetes mellitus: This led to the hypothesis that mutants display molecular adaptations resulting in the overexpression of IR isoform, which is in keeping with clinical findings reporting that some patients with type 2 diabetes mellitus who exhibit elevated levels of tyrosine phosphatase 1B (PTP1B or PTPN1) and membrane IR-associated glycoprotein PC-1 (ENPP1), which downregulate IR phosphorylation and insulin signal transduction [67].