Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival.

ABSTRACT: Mammalian pancreatic ?-cells play a pivotal role in development and glucose homeostasis through the production and secretion of insulin. Functional failure or decrease in ?-cell number leads to type 2 diabetes (T2D). Despite the physiological importance of ?-cells, the viability of ?-cells is often challenged mainly due to its poor ability to adapt to their changing microenvironment. One of the factors that negatively affect ?-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 ?-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 ?-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.

SUBMITTER: Deng Y 

PROVIDER: S-EPMC4853318 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature