Finally, a recent study in the brain hippocampus of DM rats has associated the activation of ER stress (BIP, DDIT3 and ATF4) and inflammatory stress (tumor necrosis factor (TNF) and interleukin-6 (IL6)) with reduced GLUT4 expression; furthermore, metformin/donepezil treatment was demonstrated as efficacious to reverse these alterations, becoming a promising way to manage DM-associated dementia [70]. The gene discussed is ATF4; the disease is diabetes mellitus.