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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Diabetes (New York, N.Y.) N.Y.), 2014-01, Vol.63 (1), p.216
Hauptverfasser: Alvarez-Perez, Juan Carlos, Ernst, Sara, Demirci, Cem, Casinelli, Gabriella P, Mellado-Gil, Jose Manuel D, Rausell-Palamos, Francisco, Vasavada, Rupangi C, Garcia-Ocana, Adolfo
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
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
ISSN:0012-1797
1939-327X
DOI:10.2337/db13-0333