INS and obesity due to melanocortin 4 receptor deficiency: Early animal studies suggested that FGF21, recognized as an effective insulin-sensitizing agent, may alleviate obesity-associated hyperglycemia by enhancing insulin sensitivity of hepatic and adipose tissues [10, 37, 38]; however, FGF21 levels were paradoxically elevated in insulin-resistance states [39], potentially due to either a resistance to its function or a compensatory increase in its secretion [40].