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). This evidence concerns the gene INSR and obesity due to melanocortin 4 receptor deficiency.