Details

Autor(en) / Beteiligte

• Jung, Hye Seung
• Lee, Myung-Shik

Titel

Macroautophagy in homeostasis of pancreatic β-cell

Ist Teil von

• Autophagy, 2009-02, Vol.5 (2), p.241-243

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2009

Link zum Volltext

Quelle

Taylor & Francis

Beschreibungen/Notizen

• Diabetes mellitus is characterized by decreased insulin secretion and action. Decreased insulin secretion results from a reduction in pancreatic β-cell mass and function. Apoptosis, oxidative stress, mitochondrial dysfunction and ER stress responses including JNK activation have been suggested as mechanisms of the changes of pancreatic β-cells in type 2 diabetes, however, the underlying causes were not clearly elucidated. Autophagy is an intracellular process that plays a crucial role in cellular homeostasis through degradation and recycling of organelles constitutively or in response to the environmental condition. We studied the role of autophagy in pancreatic β-cells using mice with β-cell-specific deletion of the Atg7 (autophagy-related 7) gene. Atg7-mutant mice showed increased apoptosis and decreased proliferation of β-cells with resultant reduction in β-cell mass. Pancreatic insulin content was decreased due to the decreased β-cell mass and reduced number of insulin granules. Morphological analysis of β-cells revealed accumulation of ubiquitinated proteins, swollen mitochondria, and distended ER. Insulin secretory function ex vivo was also impaired. As a result, autophagy-deficient mice showed hypoinsulinemia and hyperglycemia. These results suggest that autophagy is necessary to maintain structure, mass and function of pancreatic β-cells. Here we discuss the significance of autophagy in pancreatic β-cells with its potential relevance to the development of diabetes.