| First Author | King BC | Year | 2019 |
| Journal | Cell Metab | Volume | 29 |
| Issue | 1 | Pages | 202-210.e6 |
| PubMed ID | 30293775 | Mgi Jnum | J:272050 |
| Mgi Id | MGI:6282642 | Doi | 10.1016/j.cmet.2018.09.009 |
| Citation | King BC, et al. (2019) Complement Component C3 Is Highly Expressed in Human Pancreatic Islets and Prevents beta Cell Death via ATG16L1 Interaction and Autophagy Regulation. Cell Metab 29(1):202-210.e6 |
| abstractText | 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 beta 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 beta 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. |
