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Título

Hepatocyte growth factor/c-Met signaling is required for β-cell regeneration

AutorÁlvarez Pérez, Juan Carlos; Ernst, Sara; Demirci, Cem; Casinelli, Gabriella P.; Mellado-Gil, José Manuel ; Rausell-Palamos, Francisco; Vasavada, Rupangi C.; García-Ocaña, Adolfo
Fecha de publicaciónene-2014
EditorAmerican Diabetes Association
CitaciónDiabetes 63(1): 216-223 (2014)
ResumenHepatocyte growth factor (HGF) is a mitogen required for β-cell replication during pregnancy. To determine whether HGF/c-Met signaling is required for β-cell regeneration, we characterized mice with pancreatic deletion of the HGF receptor, c-Met (PancMet KO mice), in two models of reduced β-cell mass and regeneration: multiple low-dose streptozotocin (MLDS) and partial pancreatectomy (Ppx). We also analyzed whether HGF administration could accelerate β-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 β-cell proliferation in situations of reduced β-cell mass. Indeed, adult PancMet KO mice displayed markedly reduced β-cell replication compared with WT mice 7 days post-Ppx. Similarly, β-cell proliferation was decreased in PancMet KO mice in the MLDS mouse model. The decrease in β-cell proliferation post-Ppx correlated with a striking decrease in D-cyclin levels. Importantly, PancMet KO mice showed significantly diminished β-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 β-cell regeneration. These results indicate that HGF/c-Met signaling is critical for β-cell proliferation in situations of diminished β-cell mass and suggest that activation of this pathway can enhance β-cell regeneration. © 2014 by the American Diabetes Association.
Versión del editorhttp://dx.doi.org/10.2337/db13-0333
URIhttp://hdl.handle.net/10261/123458
DOI10.2337/db13-0333
Identificadoresissn: 0012-1797
e-issn: 1939-327X
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