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

Korean Journal of Internal Medicine 2020년 35권 6호 p.1443 ~ 1456
Quan Yi, Luo Kang, Cui Sheng, 임선우, 신유진, 고은정, 김주환, Chung Sang-J., 배수경, 정병하, 양철우,
소속 상세정보
 ( Quan Yi ) - Catholic University Transplant Research Center
 ( Luo Kang ) - Catholic University Transplant Research Center
 ( Cui Sheng ) - Catholic University Transplant Research Center
임선우 ( Lim Sun-Woo ) - Catholic University Transplant Research Center
신유진 ( Shin Yoo-Jin ) - Catholic University Transplant Research Center
고은정 ( Ko Eun-Jeong ) - Catholic University College of Medicine Seoul St. Mary’s Hospital Department of Internal Medicine
김주환 ( Kim Ju-Hwan ) - Abtis Co. Ltd.
 ( Chung Sang-J. ) - Sungkyunkwan University School of Pharmacy
배수경 ( Bae Soo-Kyung ) - Catholic University College of Pharmacy
정병하 ( Chung Byung-Ha ) - Catholic University College of Medicine Seoul St. Mary’s Hospital Department of Internal Medicine
양철우 ( Yang Chul-Woo ) - Catholic University College of Medicine Seoul St. Mary’s Hospital Department of Internal Medicine

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.

키워드

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

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