After secretion, insulin is removed from the plasma by the liver [20] in a process termed insulin clearance, which is altered in obesity [28] and models of type 2 diabetes [2, 29, 30]; the dysregulation of insulin clearance is commonly associated with obesity [31, 32] and type 2 diabetes in humans [2, 33, 34]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.