Ca²⁺/calmodulin-dependent protein kinase IV attenuates inflammation and mitochondrial dysfunction under insulin resistance in C2C12 cells

Abstract

CaMKIV has been reported involved in the improvement of whole-body insulin sensitivity and mitochondrial biogenesis of skeletal muscle. Here, we first investigate the effects of CaMKIV on glucose metabolism, cell viability, inflammatory function, and mitochondrial function in palmitate-induced C2C12 cells of insulin resistance. Then we explored the potential mechanism of these effects. Differentiated C2C12 cells were treated with or without 100 ng/ml of CaMKIV under palmitate-induced insulin resistance. The results suggest palmitate induced insulin sensitivity, reduced glucose uptake, decreased cell viability, increased inflammatory factors, and caused mitochondrial dysfunction in C2C12 cells. Of note, CaMKIV reversed palmitate-induced insulin resistance, increased the reduction of glucose uptake, inhibited inflammatory response, and mitochondrial dysfunction, despite of no change in cells viabilities. However, these beneficial effects of CaMKIV were blocked by the downregulation of CREB1. Taken together, our data demonstrated CaMKIV prevents palmitate-induced insulin resistance, inflammatory response, and mitochondrial dysfunction through phosphorylated CREB1 in differentiated C2C12 cells.

Keywords:

• CaMKIV
• mitochondrial function
• inflammation
• insulin resistance
• CREB1

Disclosure statement

The authors have no conflicts of interest associated with this manuscript.

Data availability statement

All data generated or analysed during this study are included in this article.

Additional information

Funding

This study was partly supported by funds from the National Natural Science Foundation of China [Program No. 81600619], Natural Science Foundation of Shaanxi Province [No. 708037169021] and Personal Training Special Fund of the Second Affiliated Hospital of Xi’an Jiaotong University [No. RC(XM)2016010].