| First Author | Alvarez-Perez JC | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 1 | Pages | 216-23 |
| PubMed ID | 24089510 | Mgi Jnum | J:209045 |
| Mgi Id | MGI:5565583 | Doi | 10.2337/db13-0333 |
| Citation | Alvarez-Perez JC, et al. (2014) Hepatocyte growth factor/c-Met signaling is required for beta-cell regeneration. Diabetes 63(1):216-23 |
| abstractText | Hepatocyte growth factor (HGF) is a mitogen required for beta-cell replication during pregnancy. To determine whether HGF/c-Met signaling is required for beta-cell regeneration, we characterized mice with pancreatic deletion of the HGF receptor, c-Met (PancMet KO mice), in two models of reduced beta-cell mass and regeneration: multiple low-dose streptozotocin (MLDS) and partial pancreatectomy (Ppx). We also analyzed whether HGF administration could accelerate beta-cell regeneration in wild-type (WT) mice after Ppx. Mouse islets obtained 7 days post-Ppx displayed significantly increased c-Met, suggesting a potential role for HGF/c-Met in beta-cell proliferation in situations of reduced beta-cell mass. Indeed, adult PancMet KO mice displayed markedly reduced beta-cell replication compared with WT mice 7 days post-Ppx. Similarly, beta-cell proliferation was decreased in PancMet KO mice in the MLDS mouse model. The decrease in beta-cell proliferation post-Ppx correlated with a striking decrease in D-cyclin levels. Importantly, PancMet KO mice showed significantly diminished beta-cell mass, decreased glucose tolerance, and impaired insulin secretion compared with WT mice 28 days post-Ppx. Conversely, HGF administration in WT Ppx mice further accelerated beta-cell regeneration. These results indicate that HGF/c-Met signaling is critical for beta-cell proliferation in situations of diminished beta-cell mass and suggest that activation of this pathway can enhance beta-cell regeneration. |
