INS and obesity due to melanocortin 4 receptor deficiency: Upon activation by insulin, the activated insulin receptor recruits either adaptor proteins, Grb2, or insulin receptor substrate (IRS), which in turn activates downstream ERK/p38/JNK pathways, thus regulating glucose homeostasis.[10,129] Similarly, an aberration in MAPKs signalling pathway has been implicated in the development of DM, and complications arise when the risk of developing DM is confounded by obesity (Table 2).