INS and obesity due to melanocortin 4 receptor deficiency: It is therefore possible that the previously described deficiency in autophagy in C3–KO beta-cells [20], leading to higher islet insulin content and increased insulin release from islets of beta-C3-KO mice can in the presence of HFD, produce the phenotype described here; faster weight gain, obesity, lowered insulin sensitivity, and subsequently increased beta-cell stress.