IRS1 and obesity due to melanocortin 4 receptor deficiency: Noteworthily, phosphorylated protein kinase B (p-Akt) is decreased and phosphorylated insulin receptor substrate 1 (p-IRS-1) Ser312 and phosphorylated c-Jun N-terminal protein kinase (p-JNK) are increased in skeletal muscle of patients with obesity, type 2 diabetes, and/or insulin resistance [31,32,33].