Cellular Autophagy In Alpha Cells Plays A Role In The Maintenance Of Islet Architecture

Autophagy is known to play a pivotal role in intracellular quality control through the degradation of subcellular damaged organelles and components. Whereas autophagy is essential for maintaining beta-cell function in pancreatic islets, it remains unclear as to how the cellular autophagy affects the homeostasis and function of glucagon-secreting alpha cells. To investigate the role of autophagy in alpha cells, we generated a mutant mouse model lacking Atg7, a key molecule for autophagosome formation, specifically in alpha cells. Histological analysis demonstrated more glucagon-positive cells, with a multilayered structure, in the islets under Atg7 deficiency, although metabolic profiles, such as body weight, blood glucose, and plasma glucagon levels were comparable between Atg7-deficient mice and control littermates. Consistent with our previous findings that Atg7 deficiency suppressed beta-cell proliferation, cellular proliferation was suppressed in Atg7-deficient alpha cells. These findings suggest that alpha-cell autophagy plays a role in maintaining alpha-cell area and normal islet architecture but appears to be dispensable for metabolic homeostasis. Copyright (C) 2019 Endocrine Society