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Title: PDE 5 inhibitor improves insulin sensitivity by enhancing mitochondrial function in adipocytes

Abstract

Adipocytes are involved in many metabolic disorders. It was recently reported that phosphodiesterase type 5 (PDE5) is expressed in human adipose tissue. In addition, PDE5 inhibitors have been shown to improve insulin sensitivity in humans. However, the mechanism underlying the role of PDE5 inhibitors as an insulin sensitizer remains largely unknown. The present study was undertaken to investigate the role of the PDE5 inhibitor udenafil in insulin signaling in adipocytes and whether this is mediated through the regulation of mitochondrial function. To study the mechanism underlying the insulin sensitizing action of PDE5 inhibitors, we evaluated quantitative changes in protein or mRNA levels of mitochondrial oxidative phosphorylation (OxPhos) complex, oxygen consumption rate (OCR), and fatty acid oxidation with varying udenafil concentrations in 3T3-L1 cells. Our cell study suggested that udenafil enhanced the insulin signaling pathway in 3T3-L1 cells. Following udenafil treatment, basal mitochondrial OCR, maximal OxPhos capacity, and OxPhos gene expression significantly increased. Finally, we examined whether udenafil can affect the fatty acid oxidation process. Treatment of 3T3-L1 cells with udenafil (10 and 20 μM) significantly increased fatty acid oxidation rate in a dose-dependent manner. In addition, the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) significantly increased. We demonstrated thatmore » the PDE5 inhibitor udenafil enhances insulin sensitivity by improving mitochondrial function in 3T3-L1 cells. This might be the mechanism underlying the PDE5 inhibitor-enhanced insulin signaling in adipocytes. This also suggests that udenafil may provide benefit in the treatment of type 2 diabetes and other related cardiovascular diseases. - Highlights: • Udenafil enhanced the insulin signaling pathway. • Udenafil improved mitochondrial function by increasing oxygen consumption rate (OCR). • Udenafil upregulated mitochondrial OxPhos gene expression. • Udenafil was involved in increasing fatty acid oxidation (FAO).« less

Authors:
 [1];  [2];  [2];  [1];  [1];  [1]
  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Daejeon Eulji Medical Center, Eulji University, 95, Dunsanseo-ro, Seo-gu, 35233 Daejeon (Korea, Republic of)
  2. Research Center for Endocrine and Metabolic Diseases, Chungnam National University School of Medicine, 99, Daehak-ro, Yuseong-gu, 34134, Daejeon (Korea, Republic of)
Publication Date:
OSTI Identifier:
22719131
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 493; Journal Issue: 1; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADIPOSE TISSUE; CARBOXYLIC ACIDS; CARDIOVASCULAR DISEASES; CONCENTRATION RATIO; CONSUMPTION RATES; GENES; INSULIN; MESSENGER-RNA; MITOCHONDRIA; OXIDATION; PARTIAL DIFFERENTIAL EQUATIONS; PHOSPHODIESTERASES; PHOSPHORYLATION; RECEPTORS; SENSITIVITY; SENSITIZERS

Citation Formats

Yu, Hea Min, E-mail: hmin00@naver.com, Chung, Hyo Kyun, E-mail: hkchung74@cnu.ac.kr, Kim, Koon Soon, E-mail: kunsunkim@cnu.ac.kr, Lee, Jae Min, E-mail: leejam25@eulji.ac.kr, Hong, Jun Hwa, E-mail: lammoth@eulji.ac.kr, and Park, Kang Seo, E-mail: pkkss@eulji.ac.kr. PDE 5 inhibitor improves insulin sensitivity by enhancing mitochondrial function in adipocytes. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.08.140.
Yu, Hea Min, E-mail: hmin00@naver.com, Chung, Hyo Kyun, E-mail: hkchung74@cnu.ac.kr, Kim, Koon Soon, E-mail: kunsunkim@cnu.ac.kr, Lee, Jae Min, E-mail: leejam25@eulji.ac.kr, Hong, Jun Hwa, E-mail: lammoth@eulji.ac.kr, & Park, Kang Seo, E-mail: pkkss@eulji.ac.kr. PDE 5 inhibitor improves insulin sensitivity by enhancing mitochondrial function in adipocytes. United States. doi:10.1016/J.BBRC.2017.08.140.
Yu, Hea Min, E-mail: hmin00@naver.com, Chung, Hyo Kyun, E-mail: hkchung74@cnu.ac.kr, Kim, Koon Soon, E-mail: kunsunkim@cnu.ac.kr, Lee, Jae Min, E-mail: leejam25@eulji.ac.kr, Hong, Jun Hwa, E-mail: lammoth@eulji.ac.kr, and Park, Kang Seo, E-mail: pkkss@eulji.ac.kr. Sat . "PDE 5 inhibitor improves insulin sensitivity by enhancing mitochondrial function in adipocytes". United States. doi:10.1016/J.BBRC.2017.08.140.
@article{osti_22719131,
title = {PDE 5 inhibitor improves insulin sensitivity by enhancing mitochondrial function in adipocytes},
author = {Yu, Hea Min, E-mail: hmin00@naver.com and Chung, Hyo Kyun, E-mail: hkchung74@cnu.ac.kr and Kim, Koon Soon, E-mail: kunsunkim@cnu.ac.kr and Lee, Jae Min, E-mail: leejam25@eulji.ac.kr and Hong, Jun Hwa, E-mail: lammoth@eulji.ac.kr and Park, Kang Seo, E-mail: pkkss@eulji.ac.kr},
abstractNote = {Adipocytes are involved in many metabolic disorders. It was recently reported that phosphodiesterase type 5 (PDE5) is expressed in human adipose tissue. In addition, PDE5 inhibitors have been shown to improve insulin sensitivity in humans. However, the mechanism underlying the role of PDE5 inhibitors as an insulin sensitizer remains largely unknown. The present study was undertaken to investigate the role of the PDE5 inhibitor udenafil in insulin signaling in adipocytes and whether this is mediated through the regulation of mitochondrial function. To study the mechanism underlying the insulin sensitizing action of PDE5 inhibitors, we evaluated quantitative changes in protein or mRNA levels of mitochondrial oxidative phosphorylation (OxPhos) complex, oxygen consumption rate (OCR), and fatty acid oxidation with varying udenafil concentrations in 3T3-L1 cells. Our cell study suggested that udenafil enhanced the insulin signaling pathway in 3T3-L1 cells. Following udenafil treatment, basal mitochondrial OCR, maximal OxPhos capacity, and OxPhos gene expression significantly increased. Finally, we examined whether udenafil can affect the fatty acid oxidation process. Treatment of 3T3-L1 cells with udenafil (10 and 20 μM) significantly increased fatty acid oxidation rate in a dose-dependent manner. In addition, the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) significantly increased. We demonstrated that the PDE5 inhibitor udenafil enhances insulin sensitivity by improving mitochondrial function in 3T3-L1 cells. This might be the mechanism underlying the PDE5 inhibitor-enhanced insulin signaling in adipocytes. This also suggests that udenafil may provide benefit in the treatment of type 2 diabetes and other related cardiovascular diseases. - Highlights: • Udenafil enhanced the insulin signaling pathway. • Udenafil improved mitochondrial function by increasing oxygen consumption rate (OCR). • Udenafil upregulated mitochondrial OxPhos gene expression. • Udenafil was involved in increasing fatty acid oxidation (FAO).},
doi = {10.1016/J.BBRC.2017.08.140},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 493,
place = {United States},
year = {2017},
month = {11}
}