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Hepatocyte Growth Factor/c-Met Signaling Is Required for β-Cell Regeneration

Hepatocyte 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 mas...

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Autores principales: Alvarez-Perez, Juan Carlos, Ernst, Sara, Demirci, Cem, Casinelli, Gabriella P., Mellado-Gil, Jose Manuel D., Rausell-Palamos, Francisco, Vasavada, Rupangi C., Garcia-Ocaña, Adolfo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868042/
https://www.ncbi.nlm.nih.gov/pubmed/24089510
http://dx.doi.org/10.2337/db13-0333
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author Alvarez-Perez, Juan Carlos
Ernst, Sara
Demirci, Cem
Casinelli, Gabriella P.
Mellado-Gil, Jose Manuel D.
Rausell-Palamos, Francisco
Vasavada, Rupangi C.
Garcia-Ocaña, Adolfo
author_facet Alvarez-Perez, Juan Carlos
Ernst, Sara
Demirci, Cem
Casinelli, Gabriella P.
Mellado-Gil, Jose Manuel D.
Rausell-Palamos, Francisco
Vasavada, Rupangi C.
Garcia-Ocaña, Adolfo
author_sort Alvarez-Perez, Juan Carlos
collection PubMed
description Hepatocyte 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.
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spelling pubmed-38680422015-01-01 Hepatocyte Growth Factor/c-Met Signaling Is Required for β-Cell Regeneration Alvarez-Perez, Juan Carlos Ernst, Sara Demirci, Cem Casinelli, Gabriella P. Mellado-Gil, Jose Manuel D. Rausell-Palamos, Francisco Vasavada, Rupangi C. Garcia-Ocaña, Adolfo Diabetes Islet Studies Hepatocyte 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. American Diabetes Association 2014-01 2013-12-13 /pmc/articles/PMC3868042/ /pubmed/24089510 http://dx.doi.org/10.2337/db13-0333 Text en © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Islet Studies
Alvarez-Perez, Juan Carlos
Ernst, Sara
Demirci, Cem
Casinelli, Gabriella P.
Mellado-Gil, Jose Manuel D.
Rausell-Palamos, Francisco
Vasavada, Rupangi C.
Garcia-Ocaña, Adolfo
Hepatocyte Growth Factor/c-Met Signaling Is Required for β-Cell Regeneration
title Hepatocyte Growth Factor/c-Met Signaling Is Required for β-Cell Regeneration
title_full Hepatocyte Growth Factor/c-Met Signaling Is Required for β-Cell Regeneration
title_fullStr Hepatocyte Growth Factor/c-Met Signaling Is Required for β-Cell Regeneration
title_full_unstemmed Hepatocyte Growth Factor/c-Met Signaling Is Required for β-Cell Regeneration
title_short Hepatocyte Growth Factor/c-Met Signaling Is Required for β-Cell Regeneration
title_sort hepatocyte growth factor/c-met signaling is required for β-cell regeneration
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868042/
https://www.ncbi.nlm.nih.gov/pubmed/24089510
http://dx.doi.org/10.2337/db13-0333
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