FUNDC1 modulates mitochondrial defects and pancreatic ß-cell dysfunction under lipotoxicity.
Biochem Biophys Res Commun
; 672: 54-64, 2023 09 10.
Article
em En
| MEDLINE
| ID: mdl-37336125
ABSTRACT
Insulin resistance and many metabolic disorders are causally linked to mitochondrial dysfunction or defective mitochondrial quality control. Mitophagy is a highly selective mechanism that recognizes and removes damaged mitochondria to maintain mitochondrial homeostasis. Here, we addressed the potential role of FUNDC1, a mediator of mitophagy, in pancreatic ß-cell dysfunction under lipotoxicity. In pancreatic MIN6 cells, FUNDC1 deficiency aggravated palmitate-induced mitochondrial dysfunction, which led to cell death and insulin insensitivity. Interestingly, FUNDC1 overexpression prevented these cellular harms brought on by palmitate. In mice models, pancreatic-specific FUNDC1 overexpression alleviated high-fat diet (HFD)-induced insulin resistance and obesity. Mechanistically, pancreatic-specific overexpression of FUNDC1 ameliorated mitochondrial defects and endoplasmic reticulum (ER) stress upon HFD. Our research indicates that FUNDC1 plays an essential role in apoptosis and dysfunction of pancreatic ß-cells via modulating lipotoxicity-induced mitochondrial defects.
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Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article