ADCY3 and obesity due to melanocortin 4 receptor deficiency: In mammals, there are nine closely related isoforms of ACs, and AC3 is the third member and calcium-dependent isoform.8, 9, 10 Previous studies shown that the AC3 gene expression at mRNA levels was upregulated in pancreatic islets of Goto-Kakizaki (GK) rat.11 GK rat is a hereditary non-obese animal model of T2D and exhibits a markedly reduced glucose-induced insulin release.12 The AC3 activity in the liver of ob/ob mice was increased compared with lean control mice.13 Data from these animal experiments suggested that AC3 may have a role in the pathogenesis of T2D and obesity.