| Texto completo | |
| Autor(es): Mostrar menos - |
da Silva Junior, Joel Alves
;
Vettorazzi, Jean Franciesco
;
Soriano, Sergi
;
Bru-Tari, Eva
;
Boronat-Belda, Talia
;
Castellano-Munoz, Manuel
;
Borck, Patricia Cristine
;
Ribeiro, Rosane Aparecida
;
Soares, Gabriela Moreira
;
Lubaczeuski, Camila
;
Boschero, Antonio Carlos
;
Marroqui, Laura
;
Nadal, Angel
;
Alonso-Magdalena, Paloma
;
Quesada, Ivan
;
Carneiro, Everardo Magalhaes
Número total de Autores: 16
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF NUTRITIONAL BIOCHEMISTRY; v. 146, p. 10-pg., 2025-09-11. |
| Resumo | |
The global prevalence of type 2 diabetes (T2D) continues to rise, and predictions indicate alarming records in coming decades. Although pancreatic beta- cell dysfunction and insulin resistance are key factors in the etiology of T2D, the impairment of alpha-cells has been also implicated. Hyperglucagonemia and altered suppression of glucagon release can be frequently found in individuals with T2D, contributing to hyperglycemia. Bile acids have emerged as novel signaling molecules that regulate metabolism. A wealth of evidence shows that oral treatment with the bile acid TUDCA has therapeutic benefits in T2D, primarily by improving both insulin release from beta-cells and insulin sensitivity in peripheral tissues. However, it is unknown whether TUDCA could affect other processes involved in the control of glucose metabolism. Here, we show that acute administration of TUDCA exerts a glucagonstatic action on mouse pancreatic islets and glucagon-releasing alpha TC1-9 cells. Pharmacological and/or molecular inhibition of the sphingosine-1-phosphate receptor 2 (S1PR2) and the PI3K pathway blunted the TUDCA effect on glucagon release. Additionally, TUDCA increased the activity of ATP-sensitive K+ (KATP) channels, decreased action currents and inhibited Ca2+signaling in alpha-cells without directly affecting the exocytotic process. Glucose-induced suppression of glucagon secretion was found to be compromised under hyperglycemic conditions, yet TUDCA was able to inhibit alpha-cell function, highlighting its glucagonstatic effect in a pathological context. Collectively, these findings suggest that TUDCA-induced inhibition of glucagon secretion involves the opening of alpha-cell KATP channels and activation of the S1PR2/PI3K pathway, expanding the repertoire of potential therapeutic benefits of TUDCA in diabetes treatment. (c) 2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) (AU) | |
| Processo FAPESP: | 24/09785-5 - Avançando o Conhecimento sobre os Efeitos dos Ácidos Biliares no Pâncreas Endócrino: Na Saúde, Obesidade e na Dupla Carga de Desnutrição. |
| Beneficiário: | Everardo Magalhães Carneiro |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| 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: | 17/13410-3 - Possível Contribuição do ácido tauroursodesoxicólico (TUDCA) sobre a remissão do Diabetes tipo 2 em camundongos submetidos a Derivação Duodeno Jejunal |
| Beneficiário: | Jean Franciesco Vettorazzi |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 21/02734-8 - Análise, in vitro e in vivo do mecanismo de ação do Ácido Tauroursodeoxicólico (TUDCA) sobre a morfofunção das células alpha pancreáticas e na resposta contra-regulatória do glucagon em modelo de subnutrição associado a obesidade. |
| Beneficiário: | Joel Alves da Silva Junior |
| 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 |