INS and obesity due to melanocortin 4 receptor deficiency: Mitogen-activated protein kinase phosphatase-1 (MKP-1), an enzyme expressed in the muscle, is abnormally elevated in the skeletal muscle of patients with obesity, and MKP-1 prevents phosphorylation of Akt Ser473 and signaling of molecules such as p38 AMPK, resulting in insulin resistance.