Suppression of gp130 attenuated insulin-mediated signaling and glucose uptake in skeletal muscle cells.

The aim of the present study was to investigate the effects of Oncostatin M receptor (OSMR) subunit gp130 knockdown on insulin-stimulated glucose metabolism-related signaling pathways and glucose uptake in skeletal muscle cells. siRNA-mediated gp130 knockdown was conducted in C2C12 muscle cells, and insulin was added and incubated for 1 h. The cells were cultivated to analyze the mRNA levels of gp130, phosphorylation of STAT3, and glucose metabolism-regulated signaling pathways, and OSM levels in the culture medium were analyzed. The phosphorylation of STAT 3 was significantly decreased in gp130 ^-/- cell. The insulin stimulation was significantly increased in both gp130 ^-/- and gp130 ^+/+ and the phosphorylation of IRS-1 Ser 1101 was significantly decreased in gp130 ^-/- . PI3-kinase activity and Akt Thr 308 phosphorylation were significantly decreased in gp130 ^-/- . The insulin-stimulated increase in glucose uptake rate was significantly attenuated in gp130 ^-/- . In the culture medium, OSM levels were significantly lower in gp130 ^+/+ compared to gp130 ^-/- cell. In conclusion, the knockdown of gp130 caused a decrease in STAT 3 phosphorylation and resulted in the attenuation of insulin-mediated glucose metabolism signaling in skeletal muscle cells. Thus, an excessive increase in extracellular OSM may induce blunted insulin action in skeletal muscle cells.
(© 2024. The Author(s).)