As experimentally-induced hyperglycemia and high-fat diet induced diabetes have been shown to increase ER stress and UPR activation in rodent brains (Zhao et al., 2015; Sims-Robinson et al., 2016), we studied the effect of MANF removal devoid of the hyperglycaemic effect in the brain tissue of Manffl/fl::NestinCre/+ mice. This evidence concerns the gene MANF and diabetes mellitus.