Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival
Protein & Cell
;
(12): 362-372, 2016.
Article
Dans Anglais
| WPRIM
| ID: wpr-757136
ABSTRACT
Mammalian pancreatic β-cells play a pivotal role in development and glucose homeostasis through the production and secretion of insulin. Functional failure or decrease in β-cell number leads to type 2 diabetes (T2D). Despite the physiological importance of β-cells, the viability of β-cells is often challenged mainly due to its poor ability to adapt to their changing microenvironment. One of the factors that negatively affect β-cell viability is high concentration of free fatty acids (FFAs) such as palmitate. In this work, we demonstrated that Yes-associated protein (Yap1) is activated when β-cells are treated with palmitate. Our loss- and gain-of-function analyses using rodent insulinoma cell lines revealed that Yap1 suppresses palmitate-induced apoptosis in β-cells without regulating their proliferation. We also found that upon palmitate treatment, re-arrangement of F-actin mediates Yap1 activation. Palmitate treatment increases expression of one of the Yap1 target genes, connective tissue growth factor (CTGF). Our gain-of-function analysis with CTGF suggests CTGF may be the downstream factor of Yap1 in the protective mechanism against FFA-induced apoptosis.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Pharmacologie
/
Phosphoprotéines
/
Physiologie
/
Protéines recombinantes
/
Immunohistochimie
/
Cytochalasine D
/
Actines
/
Apoptose
/
Composés hétérocycliques bicycliques
/
Acide palmitique
Limites du sujet:
Animaux
/
Humains
langue:
Anglais
Texte intégral:
Protein & Cell
Année:
2016
Type:
Article
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