Hepatocyte growth factor/c-Met signaling is required for [beta]-cell regeneration
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...
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Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2014-01, Vol.63 (1), p.216 |
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Zusammenfassung: | 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 Ppxo 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. Diabetes 2014;63:216-223 | DOI: 10.2337/db13-0333 |
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ISSN: | 0012-1797 1939-327X |
DOI: | 10.2337/db13-0333 |