Molecular and Cellular Biochemistry

, Volume 461, Issue 1–2, pp 65–72 | Cite as

Azoramide improves mitochondrial dysfunction in palmitate-induced insulin resistant H9c2 cells

  • Esma Nur Okatan
  • Yusuf Olgar
  • Erkan Tuncay
  • Belma TuranEmail author


Azoramide is identified as a new compound with the dual properties for the improvement of ER-folding capacity in various cells as well as for the treatment of T2DM. Although the effect of azoramide in glucose-homeostasis in mammalians is not known very well, a limited number of experimental studies showed that it could improve the insulin sensitivity in genetically obese mice. Therefore, here, we aimed to investigate the direct effect of azoramide on insulin signaling in insulin-resistant (IR) cardiomyocytes using IR-modelled ventricular cardiomyocytes. This model was established in H9c2 cells using palmitic acid incubation (50-μM for 24-h). The development of IR in cells was verified by monitoring the cellular 2-DG6P uptake assays in these treated cells. The 2-DG6P uptake was 50% less in the IR-cells compared to the control cells, while azoramide treatment (20-μM for 48-h) could prevent fully that decrease. In addition, azoramide treatment markedly preserved the IR-induced less ATP production and high-ROS production in these IR-cells. Furthermore, this treatment prevented the functional changes in mitochondria characterized by depolarized mitochondrial membrane potential and mitochondrial fusion or fusion-related protein levels as well as cellular ATP level. Moreover, this treatment provided marked protection against IR-associated changes in the insulin signaling pathway in cells, including recovery in the phosphorylation of IRS1 and Akt as well as the protein level of GLUT4 and Akt. Our present results, for the first time, demonstrated that azoramide plays an important protective role in IR-cardiomyocytes, at most, protective action on mitochondria. Therefore, one can suggest that azoramide, as a novel regulator, can provide direct cardioprotection in the IR-heart, at most, via affecting mitochondria and can be a good candidate as a new drug for the treatment of IR-associated cardiovascular disorders in mammalians with systemic IR.


Azoramide Insulin signaling Insulin resistance Mitochondria ROS 





Protein kinase B


Endoplasmic reticulum

GLP-1 receptor

Glucagon-like peptide-1 receptor


Glucose transporter 4


Insulin resistance


Insulin-receptor substrate protein 1


Reactive oxygen species


Type 2 diabetes



This study supported by the Scientific Research Project Fund of Cumhuriyet University under the Project number T-668 and Turkish Diabetes Foundation to ENO. BT was supported through the Project of TUBITAK SBAG-216S979.

Compliance with ethical standards

Conflict of interest

No potential conflicts of interest relevant to this article were reported.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Esma Nur Okatan
    • 1
  • Yusuf Olgar
    • 2
  • Erkan Tuncay
    • 2
  • Belma Turan
    • 2
    Email author
  1. 1.Department of Biophysics, Faculty of MedicineCumhuriyet UniversitySivasTurkey
  2. 2.Department of Biophysics, Faculty of MedicineAnkara UniversityAnkaraTurkey

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