Role of β‐cell autophagy in β‐cell physiology and the development of diabetes

Abstract Elucidating the molecular mechanism of autophagy was a landmark in understanding not only the physiology of cells and tissues, but also the pathogenesis of diverse diseases, including diabetes and metabolic disorders. Autophagy of pancreatic β‐cells plays a pivotal role in the maintenance of the mass, structure and function of β‐cells, whose dysregulation can lead to abnormal metabolic profiles or diabetes. Modulators of autophagy are being developed to improve metabolic profile and β‐cell function through the removal of harmful materials and rejuvenation of organelles, such as mitochondria and endoplasmic reticulum. Among the known antidiabetic drugs, glucagon‐like peptide‐1 receptor agonists enhance the autophagic activity of β‐cells, which might contribute to the profound effects of glucagon‐like peptide‐1 receptor agonists on systemic metabolism. In this review, the results from studies on the role of autophagy in β‐cells and their implication in the development of diabetes are discussed. In addition to non‐selective (macro)autophagy, the role and mechanisms of selective autophagy and other minor forms of autophagy that might occur in β‐cells are discussed. As β‐cell failure is the ultimate cause of diabetes and unresponsiveness to conventional therapy, modulation of β‐cell autophagy might represent a future antidiabetic treatment approach, particularly in patients who are not well managed with current antidiabetic therapy.