Exenatide promotes the autophagic function in the diabetic hippocampus: a review

Abstract

ABSTRACT The hippocampus is a vulnerable structure that can be affected by many damaging stimuli, contributing to the development of diabetic cognitive dysfunction. One of these stimuli is autophagic dysregulation. Although autophagy is a physiological process that occurs at a basal level and is considered a pro-survival mechanism, autophagic dysregulation can turn it to be a pro-death mechanism, causing hippocampal neuronal loss. Exenatide is an anti-diabetic drug that has a neuroprotective role and is reported to improve diabetic cognitive deficits. It enhances glucose-dependent insulin secretion and acts via several mechanisms, including autophagy promotion through different pathways such as the brain protein kinase A signaling pathway. This review addresses the available data about the mechanisms responsible for the autophagic dysfunction in diabetic cases, and the enhancing effect of exenatide on autophagic function. More investigations are required to elucidate the consequences of the over-stimulation, impairment, or late-stage inhibition of autophagy, and the molecular mechanisms underlying the promoting action of exenatide on the autophagic process in the diabetic hippocampus.