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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2014
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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. |
format | Online Article Text |
id | pubmed-3868042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
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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