Nucleophosmin/B23 contributes to hepatic insulin resistance through the modulation of NF- κB pathway.

Nucleophosmin/B23 contributes to hepatic insulin resistance through the modulation of NF-κB pathway. Biochem Biophys Res Commun. 2019 Feb 21;: Authors: Wang X, Ma H, Wang X Abstract Nucleophosmin (NPM)/B23 is an important nucleolar phosphoprotein involved in the regulation of assorted cellular signaling pathways. In the present study, we revealed a critical role of NPM in liver insulin resistance. NPM is markedly upregulated in insulin-resistant liver tissues and palmitic acid (PA)-exposed HepG2 cells both at mRNA and protein levels. Ectopic expression of NPM in hepatocytes aggravated PA-induced insulin resistance, lipid droplet accumulation, glucose intake impairment as well as the expression of gluconeogenic genes. Coinciding with these results, interference of NPM using small interfering RNA (siRNA) oligos ameliorated PA-induced insulin resistance, as revealed by increased phosphorylation of AKT and GSK3β following insulin treatment. As predicted, PA-triggered alterations in glucose intake and the expression of gluconeogenic enzymes were attenuated following NPM depletion. Finally, we showed that NPM plays an indispensible role in PA-induced activation of NF-κB pathway. Both of NF-κB p65 phosphorylation and nuclear translocation were impeded by NPM interference in PA-treated HepG2 cells. Taken together, these findings explicitly demonstrate that NPM participates in the development of liver insulin resistance, suggesting that N...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research