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

초록

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 beta-cells plays a pivotal role in the maintenance of the mass, structure and function of beta-cells, whose dysregulation can lead to abnormal metabolic profiles or diabetes. Modulators of autophagy are being developed to improve metabolic profile and beta-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 beta-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 beta-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 beta-cells are discussed. As beta-cell failure is the ultimate cause of diabetes and unresponsiveness to conventional therapy, modulation of beta-cell autophagy might represent a future antidiabetic treatment approach, particularly in patients who are not well managed with current antidiabetic therapy.

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