Glutathione peroxidase mimic ebselen improves glucose-stimulated insulin secretion in murine islets.

ABSTRACT:

Aims

Glutathione peroxidase (GPX) mimic ebselen and superoxide dismutase (SOD) mimic copper diisopropylsalicylate (CuDIPs) were used to rescue impaired glucose-stimulated insulin secretion (GSIS) in islets of GPX1 and(or) SOD1-knockout mice.

Results

Ebselen improved GSIS in islets of all four tested genotypes. The rescue in the GPX1 knockout resulted from a coordinated transcriptional regulation of four key GSIS regulators and was mediated by the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)-mediated signaling pathways. In contrast, CuDIPs improved GSIS only in the SOD1 knockout and suppressed gene expression of the PGC-1α pathway.

Innovation

Islets from the GPX1 and(or) SOD1 knockout mice provided metabolically controlled intracellular

SUBMITTER: Wang X 

PROVIDER: S-EPMC3887434 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature