INS and obesity due to melanocortin 4 receptor deficiency: In addition to obesity and other causes, at the molecular level, the abnormality of key proteins in the insulin signal pathway may affect cell sensitivity to insulin, such as the decrease in phosphorylated AKT, the up-regulation of phosphorylated IRS at the serine site (p-s-IRS), and the down-regulation of phosphorylated insulin receptor substrate at the tyrosine site (p-y-IRS) (Gao et al., 2002).