We have previously demonstrated that IL-22 is a powerful endogenous paracrine suppressor of oxidative and ER stress in pancreatic islets and that in obesity-induced hyperglycemia in mice, IL-22 therapy restored glucose control by attenuating defects in β-cells insulin biosynthesis and secretion5. In addition, we have also recently demonstrated that endogenous pancreatic β-cell IL-22RA1 signalling plays a crucial role in modulating β-cell health and function22. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.