Metformin acts in the gut and induces gut-liver crosstalk

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Autor(es): dc.contributorUniversidade Estadual de Campinas (UNICAMP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorBrazilian Center for Research in Energy and Materials-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorButantan Institute-
Autor(es): dc.creatorTobar, Natália-
Autor(es): dc.creatorRocha, Guilherme Z.-
Autor(es): dc.creatorSantos, Andrey-
Autor(es): dc.creatorGuadagnini, Dioze-
Autor(es): dc.creatorAssalin, Heloísa B.-
Autor(es): dc.creatorCamargo, Juliana A.-
Autor(es): dc.creatorGonçalves, Any E.S.S.-
Autor(es): dc.creatorPallis, Flavia R.-
Autor(es): dc.creatorOliveira, Alexandre G.-
Autor(es): dc.creatorRocco, Silvana A.-
Autor(es): dc.creatorNeto, Raphael M.-
Autor(es): dc.creatorde Sousa, Irene Layane-
Autor(es): dc.creatorAlborghetti, Marcos R.-
Autor(es): dc.creatorSforça, Maurício L.-
Autor(es): dc.creatorRodrigues, Patrícia B.-
Autor(es): dc.creatorLudwig, Raissa G.-
Autor(es): dc.creatorVanzela, Emerielle C.-
Autor(es): dc.creatorBrunetto, Sergio Q.-
Autor(es): dc.creatorBoer, Patrícia A.-
Autor(es): dc.creatorGontijo, José A.R.-
Autor(es): dc.creatorGeloneze, Bruno-
Autor(es): dc.creatorCarvalho, Carla R.O.-
Autor(es): dc.creatorPrada, Patricia O.-
Autor(es): dc.creatorFolli, Franco-
Autor(es): dc.creatorCuri, Rui-
Autor(es): dc.creatorMori, Marcelo A.-
Autor(es): dc.creatorVinolo, Marco A.R.-
Autor(es): dc.creatorRamos, Celso D.-
Autor(es): dc.creatorFranchini, Kleber G.-
Autor(es): dc.creatorTormena, Claudio F.-
Autor(es): dc.creatorSaad, Mario J.A.-
Data de aceite: dc.date.accessioned2025-08-21T17:13:14Z-
Data de disponibilização: dc.date.available2025-08-21T17:13:14Z-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-01-23-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1073/pnas.2211933120-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/246724-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/246724-
Descrição: dc.descriptionMetformin is the most prescribed drug for DM2, but its site and mechanism of action are still not well established. Here, we investigated the effects of metformin on basolateral intestinal glucose uptake (BIGU), and its consequences on hepatic glucose production (HGP). In diabetic patients and mice, the primary site of metformin action was the gut, increasing BIGU, evaluated through PET-CT. In mice and CaCo2 cells, this increase in BIGU resulted from an increase in GLUT1 and GLUT2, secondary to ATF4 and AMPK. In hyperglycemia, metformin increased the lactate (reducing pH and bicarbonate in portal vein) and acetate production in the gut, modulating liver pyruvate carboxylase, MPC1/2, and FBP1, establishing a gut-liver crosstalk that reduces HGP. In normoglycemia, metformin-induced increases in BIGU is accompanied by hypoglycemia in the portal vein, generating a counter-regulatory mechanism that avoids reductions or even increases HGP. In summary, metformin increases BIGU and through gut-liver crosstalk influences HGP.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionInstituto Nacional de Ciência e Tecnologia de Obesidade e Diabetes-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionDepartment of Internal Medicine School of Medical Sciences University of Campinas-
Descrição: dc.descriptionDepartment of Physical Education São Paulo State University-
Descrição: dc.descriptionBrazilian Biosciences National Laboratory Brazilian Center for Research in Energy and Materials-
Descrição: dc.descriptionDepartment of Genetics Evolution Microbiology and Immunology Institute of Biology University of Campinas-
Descrição: dc.descriptionDepartment of Biochemistry and Tissue Biology Institute of Biology University of Campinas, São Paulo-
Descrição: dc.descriptionDepartment of Structural and Functional Biology University of Campinas-
Descrição: dc.descriptionBiomedical Engineering Center University of Campinas-
Descrição: dc.descriptionInstitute Biomedical Sciences University of Sao Paulo Department of Physiology and Biophysics-
Descrição: dc.descriptionSchool of Applied Sciences University of Campinas-
Descrição: dc.descriptionButantan Institute-
Descrição: dc.descriptionDivision of Nuclear Medicine Department of Radiology School of Medical Sciences University of Campinas-
Descrição: dc.descriptionInstitute of Chemistry University of Campinas-
Descrição: dc.descriptionDepartment of Physical Education São Paulo State University-
Descrição: dc.descriptionFAPESP: 2014/50907-5-
Descrição: dc.descriptionInstituto Nacional de Ciência e Tecnologia de Obesidade e Diabetes: 465693/2014-8-
Descrição: dc.descriptionCAPES: 88882.305918/2018-1-
Idioma: dc.languageen-
Relação: dc.relationProceedings of the National Academy of Sciences of the United States of America-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectDiabetes-
Palavras-chave: dc.subjectglucose metabolism-
Palavras-chave: dc.subjectgut-liver crosstalk-
Palavras-chave: dc.subjectMetformin-
Título: dc.titleMetformin acts in the gut and induces gut-liver crosstalk-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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