期刊
CELL METABOLISM
卷 29, 期 1, 页码 202-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2018.09.009
关键词
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资金
- JDRF award [31-2008-416]
- Swedish Research Council [2009-1039]
- Knut and Alice Wallenberg Foundation
- Diabetesfonden
- Greta and Johan Kocks Foundation
- Royal Physiographical Society in Lund
- Lars Hiertas Memorial fund
- Albert Pahlsson fund
- Crafoord Foundation
- Tore Nilssons Foundation for Medical Research
- Swedish Heart-Lung Foundation [20160872]
- Swedish Foundation for Strategic Research [IRC15-0067]
We show here that human pancreatic islets highly express C3, which is both secreted and present in the cytosol. Within isolated human islets, C3 expression correlates with type 2 diabetes (T2D) donor status, HbA1c, and inflammation. Islet C3 expression is also upregulated in several rodent diabetes models. C3 interacts with ATG16L1, which is essential for autophagy. Autophagy relieves cellular stresses faced by beta cells during T2D and maintains cellular homeostasis. C3 knockout in clonal b cells impaired autophagy and led to increased apoptosis after exposure of cells to palmitic acid and IAPP. In the absence of C3, autophagosomes do not undergo fusion with lysosomes. Thus, C3 may be upregulated in islets during T2D as a cytoprotective factor against b cell dysfunction caused by impaired autophagy. Therefore, we revealed a previously undescribed intracellular function for C3, connecting the complement system directly to autophagy, with a broad potential importance in other diseases and cell types.
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