p62 is a negative regulator of ERK1, and the absence of p62 has been reported to result in insulin resistance, which coincides with earlier findings that activation of ERK1 promotes the development of obesity and diabetes.[97] However, complexities arise again when ERK1/2 signalling is reported to improve β-cell function in the pancreas via proliferation, and thereby improves insulin sensitivity.[94] Thus, ERK seems to be involved in the modulation of insulin resistance and what it contributes to the development of DM may be organ specific. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.