<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec><h3>Introduction</h3>
<p>GLP-1 receptor agonists (e.g., exenatide) are novel drugs used in the treatment of diabetes. These drugs, working with other mechanisms of action, improve glycemic control by increasing secretion of insulin and improving survival of pancreatic islet beta cells. Alterations in the oxidative stress level or the expression of proteins associated with cholesterol uptake might be responsible for those findings. Currently, there are few <italic>in vitro</italic> studies on the impact of exenatide antioxidant capacity in human islet beta cell lines and none that assess the influence of exenatide on LDL receptors and PCSK9 under hyperglycemia and oxidative stress. Therefore, we evaluated the impact of exenatide on antioxidant capacity, insulin secretion, and proteins involved in cholesterol metabolism.</p>
</sec>
<sec><h3>Materials and Method</h3>
<p>An <italic>in vitro</italic> culture of insulin-secreting cells 1.1E7 was subjected to hyperglycemia and oxidative stress. Assessment was made of the expression of enzymes associated with oxidative stress (NADPH oxidase, catalase, glutathione peroxidase, superoxide dismutase, iNOS) and cholesterol uptake (LDL receptors, PCSK9). Additionally, insulin and nitrite levels in culture media were quantified.</p>
</sec>
<sec><h3>Results</h3>
<p>We showed that exenatide improves expression of catalase and reduces the amount of nitrite in cell cultures in a protein kinase A–dependent manner. Those results were accompanied by a drop in the expression of LDL receptors and PCSK9. Insulin secretion was modestly increased in the culture condition.</p>
</sec>
<sec><h3>Conclusions</h3>
<p>Our findings show potential protective mechanisms exerted by exenatide in human insulin-secreting pancreatic beta cell line (1.1E7), which may be exerted through increased antioxidant capacity and reduced accumulation of cholesterol.</p>
</sec>
</abstract>

Introduction
GLP-1 receptor agonists (e.g., exenatide) are novel drugs used in the treatment of diabetes. These drugs, working with other mechanisms of action, improve glycemic control by increasing secretion of insulin and improving survival of pancreatic islet beta cells. Alterations in the oxidative stress level or the expression of proteins associated with cholesterol uptake might be responsible for those findings. Currently, there are few in vitro studies on the impact of exenatide antioxidant capacity in human islet beta cell lines and none that assess the influence of exenatide on LDL receptors and PCSK9 under hyperglycemia and oxidative stress. Therefore, we evaluated the impact of exenatide on antioxidant capacity, insulin secretion, and proteins involved in cholesterol metabolism.

Materials and Method
An in vitro culture of insulin-secreting cells 1.1E7 was subjected to hyperglycemia and oxidative stress. Assessment was made of the expression of enzymes associated with oxidative stress (NADPH oxidase, catalase, glutathione peroxidase, superoxide dismutase, iNOS) and cholesterol uptake (LDL receptors, PCSK9). Additionally, insulin and nitrite levels in culture media were quantified.

Results
We showed that exenatide improves expression of catalase and reduces the amount of nitrite in cell cultures in a protein kinase A–dependent manner. Those results were accompanied by a drop in the expression of LDL receptors and PCSK9. Insulin secretion was modestly increased in the culture condition.

Conclusions
Our findings show potential protective mechanisms exerted by exenatide in human insulin-secreting pancreatic beta cell line (1.1E7), which may be exerted through increased antioxidant capacity and reduced accumulation of cholesterol.

Exenatide improves antioxidant capacity and reduces the expression of LDL receptors and PCSK9 in human insulin-secreting 1.1E7 cell line subjected to hyperglycemia and oxidative stress

Department of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice

Postępy Higieny i Medycyny Doświadczalnej

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Introduction
GLP-1 receptor agonists (e.g., exenatide) are novel drugs used in the treatment of diabetes. These drugs, working with other mechanisms of action,...

Exenatide improves antioxidant capacity and reduces the expression of LDL receptors and PCSK9 in human insulin-secreting 1.1E7 cell line subjected to hyperglycemia and oxidative stress

Article Category: Original Article

Published Online: Feb 20, 2022

Page range: 16 - 23

Received: Jan 01, 2021

Accepted: Jul 16, 2021

DOI: https://doi.org/10.2478/ahem-2021-0037

Keywords
Exenatide, GLP-1, pancreatic beta cell, oxidative stress, insulin, PCSK9, LDL receptor

© 2022 Łukasz Bułdak et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig. 1

Fig. 2

Fig. 3

Exenatide improves antioxidant capacity and reduces the expression of LDL receptors and PCSK9 in human insulin-secreting 1.1E7 cell line subjected to hyperglycemia and oxidative stress

Article Category: Original Article

Published Online: Feb 20, 2022

Page range: 16 - 23

Received: Jan 01, 2021

Accepted: Jul 16, 2021

DOI: https://doi.org/10.2478/ahem-2021-0037

KeywordsExenatide, GLP-1, pancreatic beta cell, oxidative stress, insulin, PCSK9, LDL receptor

© 2022 Łukasz Bułdak et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig. 1

Fig. 2

Fig. 3

Keywords
Exenatide, GLP-1, pancreatic beta cell, oxidative stress, insulin, PCSK9, LDL receptor