| Texto completo | |
| Autor(es): |
Soares, Gabriela M.
;
Balbo, Sandra L.
;
Bronczek, Gabriela A.
;
Vettorazzi, Jean F.
;
Marmentini, Carine
;
Zangerolamo, Lucas
;
Velloso, Licio A.
;
Carneiro, Everardo M.
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM; v. 326, n. 2, p. 14-pg., 2024-02-20. |
| Resumo | |
Vertical sleeve gastrectomy (VSG) restores glucose homeostasis in obese mice and humans. In addition, the increased fibroblast growth factor (FGF)15/19 circulating level postsurgery has been implicated in this effect. However, the impact of FGF15/19 on pancreatic islets remains unclear. Using a diet-induced obese mice model, we demonstrate that VSG attenuates insulin hypersecretion in isolated pancreatic islets, likely due to morphological alterations in the endocrine pancreas such as reduction in islet, beta-cell, and alpha-cell mass. In addition, VSG relieves gene expression of endoplasmic reticulum (ER) stress and inflammation markers in islets from obese mice. Incubation of INS-1E beta-cells with serum from obese mice induced dysfunction and cell death, whereas these conditions were not induced with serum from obese mice submitted to VSG, implicating the involvement of a humoral factor. Indeed, VSG increased FGF15 circulating levels in obese mice, as well as the expression of FGF receptor 1 (Fgfr1) and its coreceptor beta-klotho (Klb), both in pancreatic islets from VSG mice and in INS-1E cells treated with the serum from these mice. Moreover, exposing INS-1E cells to an FGFR inhibitor abolished the effects of VSG serum on insulin secretion and cell death. Also, recombinant FGF19 prevents INS-1E cells from dysfunction and death induced by serum from obese mice. These findings indicate that the amelioration of glucose-insulin homeostasis promoted by VSG is mediated, at least in part, by FGF15/19. Therefore, approaches promoting FGF15/19 release or action may restore pancreatic islet function in obesity. (AU) | |
| Processo FAPESP: | 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas |
| Beneficiário: | Licio Augusto Velloso |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs |
| Processo FAPESP: | 19/00728-0 - Papel da inter-relação intestino-pâncreas na manutenção da homeostase glicêmica de camundongos obesos submetidos à gastrectomia vertical: uma abordagem molecular e funcional |
| Beneficiário: | Gabriela Moreira Soares |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 18/26080-4 - Caracterização dos mecanismos moleculares e funcionais envolvidos nas disfunções endócrino-metabólicas, cardiovasculares e neurais induzidas pela restrição de aminoácidos in vitro e in vivo: possível papel terapêutico do ácido biliar TUDCA |
| Beneficiário: | Everardo Magalhães Carneiro |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |