| Texto completo | |
| Autor(es): |
Araujo, Thiago dos Reis
;
da Silva Junior, Joel Alves
;
Alves, Bruna Lourenconi
;
Guimaraes, Dimitrius Santiago Passos Simoes Froes
;
Barreto, Lohanna Monali
;
Muniz, Mariana Roberta Rodrigues
;
Rieusset, Jennifer
;
Carneiro, Everardo Magalhaes
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | METABOLISM-CLINICAL AND EXPERIMENTAL; v. 173, p. 13-pg., 2025-12-01. |
| Resumo | |
Aims/hypothesis: Nutritional disorders directly affect the endocrine pancreas, increasing the susceptibility to type 2 diabetes mellitus. However, the molecular mechanisms underlying these alterations remain unknown. This study aims to characterize the role of endoplasmic reticulum (ER)-mitochondria contact sites, known as mitochondrial-associated membranes (MAMs), in insulin secretion dysfunctions associated with undernutrition, obesity, and the double burden of malnutrition (DBM). Methods: Rat pancreatic INS-1E beta-cells were cultured in a medium without amino acids supplemented with 1 x (control) or 0.25 x (amino acid restriction) of an amino acid solution for 48 h, and then cells were exposed to a fatty acid mix for 48 h. Male C57BL/6 mice were fed a normoprotein diet (14 % protein) or protein-restricted diet (6 % protein) for 6 weeks and subsequently a high-fat diet (35 % kcal) for 12 weeks. ER-mitochondria interactions were evaluated by in situ proximity ligation assay and transmission electronic microscopy. Results: Our findings indicate that protein restriction reduces ER-mitochondria contacts in pancreatic beta-cells, leading to decreased mitochondrial metabolism and glucose-stimulated insulin secretion (GSIS). In contrast, obesity increases ER-mitochondria contact points, mitochondrial metabolism, and GSIS in pancreatic beta-cells, without alterations in viability. DBM results in a significant increase in ER-mitochondria contacts, elevated mitochondrial calcium levels, increased production of reactive oxygen species, and cell death, collectively contributing to impaired GSIS response in the context of obesity. Conclusions/interpretation: These data indicates that MAMs play a crucial role in GSIS during nutritional disorders such as undernutrition, obesity, and DBM. Importantly, changes in MAMs precede GSIS impairment, therefore targeting these interactions might prevent further disruption in beta-cell function. (AU) | |
| Processo FAPESP: | 17/24851-0 - Análise, in vitro e in vivo, do mecanismo de ação do ácido tauroursodeoxicólico (TUDCA) sobre a função mitocondrial das ilhotas pancreáticas e tecidos insulino-responsivos submetidos à restrição de aminoácidos em associação com ácidos graxos |
| Beneficiário: | Thiago dos Reis Araujo |
| Modalidade de apoio: | Bolsas no Brasil - 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 |