A role for Glucagon-Like Peptide-1 in the regulation of beta-cell autophagy

Autophagy is a highly conserved intracellular recycling pathway that serves to recycle damaged organelles/proteins or superfluous nutrients during times of nutritional stress to provide energy to maintain intracellular homeostasis and sustain core metabolic functions. Under these conditions, autophagy functions as a cell survival mechanism but impairment of this pathway can lead to pro-death stimuli. Due to their role in synthesising and secreting insulin, pancreatic beta-cells have a high requirement for robust degradation pathways. Recent research suggests that functional autophagy is required to maintain beta-cell survival and function in response to high fat diet suggesting a pro-survival role. However, a role for autophagy has also been implicated in the pathogenesis of type 2 diabetes. Thus, the pro-survival vs pro-death role of autophagy in regulating beta-ell mass requires discussion. Emerging evidence suggests that Glucagon-Like Peptide-1 (GLP-1) may exert beneficial effects on glucose homeostasis via autophagy-dependent pathways both in pancreatic beta-cells and in other cell types. The aim of the current review is to: i) summarise the literature surrounding beta-cell autophagy and its pro-death vs prosurvival role in regulating beta-cell mass; ii) review the literature describing the impact of GLP-1 on beta-cell autophagy and in other cell types; iii) discuss the potential underlying mechanisms.