Korean J Intern Med.  2020 Nov;35(6):1443-1456. 10.3904/kjim.2019.269.

The therapeutic efficacy of water-soluble coenzyme Q10 in an experimental model of tacrolimus-induced diabetes mellitus

• Quan Y
• Luo K
• Cui S
• Lim SW
• Shin YJ
• Ko EJ
• Kim JH
• Chung SJ
• Bae SK
• Chung BH
• Yang CW

• KMID: 2508140
• DOI: http://doi.org/10.3904/kjim.2019.269

Abstract

Background/Aims
Coenzyme Q10 (CoQ₁₀) has antioxidant effects and is commercially available and marketed extensively. However, due to its low bioavailability, its effects are still controversial. We developed a water-soluble CoQ₁₀-based micelle formulation (CoQ₁₀-W) and tested it in an experimental model of tacrolimus (TAC)-induced diabetes mellitus (DM).
Methods
We developed CoQ₁₀-W from a glycyrrhizic-carnitine mixed layer CoQ₁₀ micelle preparation based on acyltransferases. TAC-induced DM rats were treated with either lipid-soluble CoQ₁₀ (CoQ₁₀-L) or CoQ₁₀-W for 4 weeks. Their plasma and pancreatic CoQ₁₀ concentrations were measured using liquid chromatography- tandem mass spectrometry. The therapeutic efficacies of CoQ₁₀-W and CoQ₁₀-L on TAC-induced DM were compared using functional and morphological parameters and their effects on cell viability and reactive oxygen species (ROS) production were also evaluated in cultured rat insulinoma cells.
Results
The plasma CoQ₁₀ level was significantly increased in the CoQ₁₀-W group compared to that in the CoQ₁₀-L group. Intraperitoneal glucose tolerance tests and glucose-stimulated insulin secretion revealed that CoQ₁₀-W controlled hyperglycemia and restored insulin secretion significantly better than CoQ₁₀-L. The TAC-mediated decrease in pancreatic islet size was significantly attenuated by CoQ₁₀-W but not by CoQ₁₀-L. TAC-induced oxidative stress and apoptosis were significantly more reduced by CoQ₁₀-W than CoQ₁₀-L. Electron microscopy revealed that CoQ₁₀-W restored TAC-induced attenuation in the number of insulin granules and the average mitochondrial area, unlike CoQ₁₀-L. In vitro studies showed that CoQ₁₀-L and CoQ₁₀-W both improved cell viability and reduced ROS production in TAC-treated islet cells to a similar extent.
Conclusions
CoQ₁₀-W has better therapeutic efficacy than CoQ₁₀-L in TAC-induced DM.

Keyword

Coenzyme Q10; Tacrolimus; Diabetes mellitus; Oxidative stress; Apoptosis