Unknown

Dataset Information

0

Salsalate and Adiponectin Improve Palmitate-Induced Insulin Resistance via Inhibition of Selenoprotein P through the AMPK-FOXO1? Pathway.


ABSTRACT: Selenoprotein P (SeP) was recently identified as a hepatokine that induces insulin resistance (IR) in rodents and humans. Recent clinical trials have shown that salsalate, a prodrug of salicylate, significantly lowers blood glucose levels and increases adiponectin concentrations. We examined the effects of salsalate and full length-adiponectin (fAd) on the expression of SeP under hyperlipidemic conditions and explored their regulatory mechanism on SeP. In palmitate-treated HepG2 cells as well as high fat diet (HFD)-fed male Spraque Dawley (SD) rats and male db/db mice, SeP expression and its regulatory pathway, including AMPK-FOXO1?, were evaluated after administration of salsalate and salicylate. Palmitate treatment significantly increased SeP expression and aggravated IR, while knock-down of SeP by siRNA restored these changes in HepG2 cells. Palmitate-induced SeP expression was inhibited by both salsalate and salicylate, which was mediated by AMPK activation, and was blocked by AMPK siRNA or an inhibitor of AMPK. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift (EMSA) assay showed that salsalate suppressed SeP expression by AMPK-mediated phosphorylation of FOXO1?. Moreover, fAd also reduced palmitate-induced SeP expression through the activation of AMPK, which results in improved IR. Both salsalate and salicylate treatment significantly improved glucose intolerance and insulin sensitivity, accompanied by reduced SeP mRNA and protein expression in HFD-fed rats and db/db mice, respectively. Taken together, we found that salsalate and adiponectin ameliorated palmitate-induced IR in hepatocytes via SeP inhibition through the AMPK-FOXO1? pathway. The regulation of SeP might be a novel mechanism mediating the anti-diabetic effects of salsalate and adiponectin.

SUBMITTER: Jung TW 

PROVIDER: S-EPMC3689003 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

altmetric image

Publications

Salsalate and Adiponectin Improve Palmitate-Induced Insulin Resistance via Inhibition of Selenoprotein P through the AMPK-FOXO1α Pathway.

Jung Tae Woo TW   Choi Hae Yoon HY   Lee So Young SY   Hong Ho Cheol HC   Yang Sae Jeong SJ   Yoo Hye Jin HJ   Youn Byung-Soo BS   Baik Sei Hyun SH   Choi Kyung Mook KM  

PloS one 20130618 6


Selenoprotein P (SeP) was recently identified as a hepatokine that induces insulin resistance (IR) in rodents and humans. Recent clinical trials have shown that salsalate, a prodrug of salicylate, significantly lowers blood glucose levels and increases adiponectin concentrations. We examined the effects of salsalate and full length-adiponectin (fAd) on the expression of SeP under hyperlipidemic conditions and explored their regulatory mechanism on SeP. In palmitate-treated HepG2 cells as well as  ...[more]

Similar Datasets

| S-EPMC5431091 | biostudies-literature
| S-EPMC9060971 | biostudies-literature
| S-EPMC9171728 | biostudies-literature
| S-EPMC8614693 | biostudies-literature
| S-EPMC10722847 | biostudies-literature
| S-EPMC4007721 | biostudies-other
| S-EPMC4083475 | biostudies-literature
| S-EPMC3387563 | biostudies-literature
2016-11-03 | GSE52048 | GEO
| S-EPMC5698464 | biostudies-literature