[HTML][HTML] Loss of autophagy diminishes pancreatic β cell mass and function with resultant hyperglycemia

HS Jung, KW Chung, JW Kim, J Kim, M Komatsu… - Cell metabolism, 2008 - cell.com
HS Jung, KW Chung, JW Kim, J Kim, M Komatsu, K Tanaka, YH Nguyen, TM Kang, KH Yoon…
Cell metabolism, 2008cell.com
Autophagy is a cellular degradation-recycling system for aggregated proteins and damaged
organelles. Although dysregulated autophagy is implicated in various diseases including
neurodegeneration, its role in pancreatic β cells and glucose homeostasis has not been
described. We produced mice with β cell-specific deletion of Atg7 (autophagy-related 7).
Atg7 mutant mice showed impaired glucose tolerance and decreased serum insulin level. β
cell mass and pancreatic insulin content were reduced because of increased apoptosis and …
Summary
Autophagy is a cellular degradation-recycling system for aggregated proteins and damaged organelles. Although dysregulated autophagy is implicated in various diseases including neurodegeneration, its role in pancreatic β cells and glucose homeostasis has not been described. We produced mice with β cell-specific deletion of Atg7 (autophagy-related 7). Atg7 mutant mice showed impaired glucose tolerance and decreased serum insulin level. β cell mass and pancreatic insulin content were reduced because of increased apoptosis and decreased proliferation of β cells. Physiological studies showed reduced basal and glucose-stimulated insulin secretion and impaired glucose-induced cytosolic Ca2+ transients in autophagy-deficient β cells. Morphologic analysis revealed accumulation of ubiquitinated protein aggregates colocalized with p62, which was accompanied by mitochondrial swelling, endoplasmic reticulum distension, and vacuolar changes in β cells. These results suggest that autophagy is necessary to maintain structure, mass and function of pancreatic β cells, and its impairment causes insulin deficiency and hyperglycemia because of abnormal turnover and function of cellular organelles.
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