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

• Published in: Biochemical and biophysical research communications Vol. 493; no. 1; pp. 631 - 636
• Main Authors: Yu, Hea Min, Chung, Hyo Kyun, Kim, Koon Soon, Lee, Jae Min, Hong, Jun Hwa, Park, Kang Seo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.11.2017
• Subjects: 3T3-L1 Cells; 60 APPLIED LIFE SCIENCES; Adipocyte; Adipocytes - drug effects; Adipocytes - physiology; ADIPOSE TISSUE; Animals; CARBOXYLIC ACIDS; CARDIOVASCULAR DISEASES; CONCENTRATION RATIO; CONSUMPTION RATES; Dose-Response Relationship, Drug; Fatty Acids - metabolism; GENES; INSULIN; Insulin - administration & dosage; Insulin Resistance - physiology; Insulin sensitivity; MESSENGER-RNA; Mice; MITOCHONDRIA; Mitochondria - drug effects; Mitochondria - physiology; Mitochondrial function; OXIDATION; Oxygen Consumption - drug effects; Oxygen Consumption - physiology; PARTIAL DIFFERENTIAL EQUATIONS; PDE5 inhibitor; Phosphodiesterase 5 Inhibitors - administration & dosage; PHOSPHODIESTERASES; PHOSPHORYLATION; Pyrimidines - administration & dosage; RECEPTORS; SENSITIVITY; SENSITIZERS; Sulfonamides - administration & dosage; Adipocyte; Insulin sensitivity; Mitochondrial function; PDE5 inhibitor
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.08.140

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. •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).