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

The biology of autophagy in health and disease conditions has been intensively analyzed for decades. Several potential interventions can induce autophagy in preclinical research; however, none of these interventions are ready for translation to clinical practice yet. The topic of the current review is the molecular regulation of autophagy by glucagon, glucagon-like peptide (GLP)-1 and the GLP-1-degrading enzyme dipeptidyl peptidase-4 (DPP-4). Glucagon is a well-known polypeptide that induces autophagy. In contrast, GLP-1 has been shown to inhibit glucagon secretion; GLP-1 also has been related to the induction of autophagy. DPP-4 inhibitors can induce autophagy in a GLP-1-dependent manner, but other diverse effects could be relevant. Here, we analyze the distinct molecular regulation of autophagy by glucagon, GLP-1, and DPP-4 inhibitors. Additionally, the potential contribution to autophagy by glucagon and GLP-1 after bariatric surgery is discussed.