CKM and obesity due to melanocortin 4 receptor deficiency: To address the current controversy, we analyzed two mouse models of T2DM that may represent different disease mechanisms: obesity-dependent db/db mice, expressing a spontaneous mutation in the leptin receptor (Leprdb), and obesity-independent MKR mice, expressing the human insulin-like growth factor I receptor (IGF-1R) gene containing the K1003R mutation driven by the murine creatine kinase, muscle (Ckm) promoter.