Main content area

SAD-A, a downstream mediator of GLP-1 signaling, promotes the phosphorylation of Bad S155 to regulate in vitro β-cell functions

Wang, Kai, Liu, Dechen, Zhang, Yaqin, Chang, Xiaoai, Xu, Rufeng, Pang, Jing, Li, Kai, Sun, Peng, Zhu, Yunxia, Han, Xiao
Biochemical and biophysical research communications 2019 v.509 no.1 pp. 76-81
apoptosis, glucagon-like peptide 1, islets of Langerhans, noninsulin-dependent diabetes mellitus, patients, phosphorylation, secretin, secretion
The incretin hormone GLP-1 reduces β-cell failure in patients with type 2 diabetes. Previous studies demonstrated that GLP-1 activates SAD-A, a member of the AMPK family, to regulate glucose-stimulated secretion (GSIS), but the underlying mechanisms of SAD-A regulation of β-cell functions remain poorly understood. Here, we propose that activation of SAD-A by GLP-1 promotes the phosphorylation of Bad S155, which in turn positively affects GSIS and β-cell survival. Bad therefore appears to be a downstream molecule of a SAD-A pathway that mediates the GLP-1-triggered reduction in β-cell failure. Knockdown of endogenous SAD-A expression significantly exacerbated in vitro β-cell dysfunction under lipotoxic conditions and promoted lipotoxicity-induced apoptosis, whereas overexpression of SAD-A inhibited β-cell apoptosis. SAD-A silencing increased ER stress and inhibited the autophagic flux, which contributed to β-cell apoptosis. Thus, SAD-A appears to function as a downstream molecule of GLP-1 signaling that results in Bad S155 phosphorylation. This phosphorylation might therefore be involved in the GLP-1-linked protection against β-cell dysfunction and apoptosis.