INS and obesity due to melanocortin 4 receptor deficiency: 5-HT2CR knockout mice in hypothalamus produces insulin resistance and type 2 diabetes, with hyperphagia, obesity, hyperinsulinemia, and impaired glucose tolerance (Zhou et al., 2007; Xu et al., 2008; Xu et al., 2010), where 5-HT2CR agonists are effective in improving glucose tolerance and hyperinsulinemia in murine models of obesity and insulin resistance (Zhou et al., 2007; Higgins et al., 2015; Burke et al., 2017), suggesting that 5-HT2CR is involved in improving insulin sensitivity and hyperinsulinemia.