Relevance of Autophagy Induction by Gastrointestinal Hormones: Focus on the Incretin-Based Drug Target and Glucagon

Kanasaki, Keizo; Kawakita, Emi; Koya, Daisuke

GLP-1 can protect β cells from insults induced by chronic exposure to excess nutrients via induction of autophagosomallysosomal fusion (Zummo et al., 2017; Arden, 2018) . Exendin-4, an agonistic polypeptide for human GLP-1R derived from the venom of the Gila monster lizard, has also been shown to enhance lysosomal function in β-cells, improve autophagosome clearance and protect against islet injury in a rat model of tacrolimus-induced diabetes (Lim et al., 2016) . Indeed, in this study, β cells from rats administered Exendin-4 showed a reduction in the number of autophagosomes (Lim et al., 2016) . Therefore, in certain environments, contrary to the hypothesis of the antiglucagon and antiautophagic signaling effects of GLP-1, GLP-1 receptor signaling could be relevant to the accelerated effects on autophagosomal-lysosomal fusion and the positive mediation of autophagic flux. However, the role of GLP-1 in β-cell autophagy is complex and likely dependent on stress conditions. In a rat model fed with high levels of fructose, GLP-1 analog intervention induced notable inhibition of β cell autophagy and enhanced β cell mass and function (Maiztegui et al., 2017) . The detailed molecular regulation of the autophagy system in β cells via GLP-1 receptor signaling requires further investigation.