biostudies-literatureHimuro MJapan Agency for Medical Research and DevelopmentDaiichi-SankyoJapan Society for the Promotion of Science1979-1992https://www.ebi.ac.uk/biostudies/studies/S-EPMC6786006biostudies-literatureUnknown3(11)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 β-cell function in pancreatic islets, it remains unclear as to how the cellular autophagy affects the homeostasis and function of glucagon-secreting α cells. To investigate the role of autophagy in α cells, we generated a mutant mouse model lacking Atg7, a key molecule for autophagosome formation, specifically in α 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 β-cell proliferation, cellular proliferation was suppressed in Atg7-deficient α cells. These findings suggest that α-cell autophagy plays a role in maintaining α-cell area and normal islet architecture but appears to be dispensable for metabolic homeostasis.Journal of the Endocrine SocietyCellular Autophagy in α Cells Plays a Role in the Maintenance of Islet Architecture.PMC6786006JP18gm061000516K1549017K0984817H04202Shiota CWatada HMiura MSasaki SSuzuki LGittes GKKatahira TFujitani YGoto HHimuro MMiyatsuka TKoike MNishida YfalseCellular Autophagy in α 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 β-cell function in pancreatic islets, it remains unclear as to how the cellular autophagy affects the homeostasis and function of glucagon-secreting α cells. To investigate the role of autophagy in α cells, we generated a mutant mouse model lacking Atg7, a key molecule for autophagosome formation, specifically in α 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 β-cell proliferation, cellular proliferation was suppressed in Atg7-deficient α cells. These findings suggest that α-cell autophagy plays a role in maintaining α-cell area and normal islet architecture but appears to be dispensable for metabolic homeostasis.2019-01-01T00:00:00Z2019 Nov2024-11-20T05:42:25.091Z2019-11-05T08:11:18ZS-EPMC67860063162066810.1210/js.2019-00075