Moreover, our findings demonstrate that the lack of endogenous CORT (cort−/− mice) prevents the up-regulation of all components of the pancreatic ghrelin system as well as insulin secretion (mRNA expression and release) induced by obesity in cort+/+ mice, thereby suggesting that endogenous CORT may be a key regulator of pancreatic endocrine function under normal and particularly under pathophysiological states (obesity). Here, CORT is linked to obesity due to melanocortin 4 receptor deficiency.