| Texto completo | |
| Autor(es): |
Villaca, Catharina B. P.
;
Oliveira, Viviane R.
;
Santos, Gustavo J.
;
Ortis, Fernanda
Número total de Autores: 4
|
| Tipo de documento: | Artigo Científico |
| Fonte: | ISLETS; v. 17, n. 1, p. 18-pg., 2025-12-31. |
| Resumo | |
HNF4 alpha is important for beta cells' ability to adequately secrete insulin in response to glucose concentration and endoplasmic reticulum (ER) homeostasis. In humans, HNF4 alpha mutations are responsible for Diabetes mellitus subtype MODY1, which has an age-determining onset. Additionally, in other forms of DM, there is evidence that sex can influence beta cell dysfunction, with possible involvement of ER stress pathways. Thus, we assessed the influence of sex and age on beta-cell dysfunction induced by HNF4 alpha absence. We used an animal model with specific beta cells KO of HNF4 alpha, induced after birth (Ins. CRE HNF4 alpha loxP/loxP). Glucose intolerance is observed after 10 d of KO induction, at 50 d of age, with KO males (MKO) displaying more severe glucose intolerance than KO females (FKO). The percentage of insulin-positive cells in KO mice islets is lower compared to Control at all ages evaluated, with MKO mice showing a more pronounced decline at later ages compared to FKO. Both KO groups exhibited reduced beta cell mass and increased alpha-cell mass, which was more pronounced in MKO. ER stress was induced in both KO groups; however, ER stress-mediated apoptosis was observed only in MKO. FKO mice show evidence of beta cell differentiated state loss. In summary, beta cell loss in HNF4 alpha-KO is influenced by sex and age, involves induction of ER stress, and is more severe in males, where ER stress-induced beta cell death is observed. Partial protection observed in females seems to involve dedifferentiation of beta cells. (AU) | |
| Processo FAPESP: | 14/50867-3 - INCT 2014: Instituto Nacional de Ciência e Tecnologia de Bioanalítica |
| Beneficiário: | Marco Aurelio Zezzi Arruda |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 17/04580-2 - Estudo da destruição de células beta pancreáticas: o papel de NF-kB, HNF4a e IL6 no desenvolvimento do Diabetes mellitus |
| Beneficiário: | Fernanda Ortis |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/26062-9 - Avaliar o fator de transcrição HNF4± na função, viabilidade e estado diferenciado das células beta em diferentes condições que podem levar ao desenvolvimento do Diabetes Mellitus |
| Beneficiário: | Fernanda Ortis |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |