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BMC Endocrine Disorders
Published in: BMC Endocrine Disorders 1/2020

01-12-2020 | Insulins | Research article

In vitro treatment of 3 T3-L1 adipocytes with recombinant Calcium/calmodulin-dependent Protein Kinase IV (CaMKIV) limits ER stress and improves insulin sensitivity through inhibition of autophagy via the mTOR/CREB signaling pathway

Authors: Jiali Liu, Ruihua Yang, Hao Meng, Ting Zhou, Qian He

Published in: BMC Endocrine Disorders | Issue 1/2020

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Abstract

Background

Recently, CaMKIV has been identified as a potential regulator of skeletal muscle glucose metabolism, it can also affect insulin gene expression in pancreas. However, its effects on adipose insulin resistance have yet to be explored. Autophagy has been shown as a potential therapeutic target for ER (endoplasmic reticulum) stress and insulin resistance. The purpose of this study is to investigate the effects of CaMKIV on ER stress, autophagic function and insulin signaling in tunicamycin-treated adipocytes.

Methods

In this study, mature 3 T3-L1 adipocytes were treated with tunicamycin to induce ER stress. Tunicamycin-treated 3 T3-L1 adipocytes were treated with recombinant CaMKIV in the presence or absence of targeted-siRNA mediated down-regulation of CREB and mTOR. The ER stress markers, autophagy activation, mTOR/CREB signaling and insulin sensitivity were analyzed by western blotting or electron microscopy.

Results

Treatment with CaMKIV significantly reversed tunicamycin-induced expression of p-PERK, cleaved-ATF6, Atg7 and LC3II. It also reduced p62 expression. In addition, levels of p-Akt and p-IRS-1 were increased. Moreover, CaMKIV inhibited activated ER stress and insulin resistance in Atg7 siRNA transfected adipocytes. However, the protective effects of CaMKIV on ER stress, insulin signaling, and autophagy function were nullified by suppression of mTOR or CREB in tunicamycin-treated adipocytes.

Conclusion

This study proves recombinant CaMKIV inhibits tunicamycin-induced ER stress and insulin resistance by regulating autophagy. The protective effect of CaMKIV in adipocytes is affected at least partly through mTOR/CREB signaling. Our finding may offer novel opportunities for treating obesity and type 2 diabetes.
Appendix
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Metadata
Title
In vitro treatment of 3 T3-L1 adipocytes with recombinant Calcium/calmodulin-dependent Protein Kinase IV (CaMKIV) limits ER stress and improves insulin sensitivity through inhibition of autophagy via the mTOR/CREB signaling pathway
Authors
Jiali Liu
Ruihua Yang
Hao Meng
Ting Zhou
Qian He
Publication date
01-12-2020
Publisher
BioMed Central
Keywords
Insulins
Insulins
Published in
BMC Endocrine Disorders / Issue 1/2020
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-020-00589-2

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