PMID- 28888986
OWN - NLM
STAT- MEDLINE
DCOM- 20171023
LR  - 20220331
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 493
IP  - 1
DP  - 2017 Nov 4
TI  - PDE 5 inhibitor improves insulin sensitivity by enhancing mitochondrial function 
      in adipocytes.
PG  - 631-636
LID - S0006-291X(17)31663-7 [pii]
LID - 10.1016/j.bbrc.2017.08.140 [doi]
AB  - 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 muM) 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-1alpha) 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.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Yu, Hea Min
AU  - Yu HM
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Daejeon Eulji Medical Center, Eulji University, 95, Dunsanseo-ro, Seo-gu, 35233 
      Daejeon, Republic of Korea. Electronic address: hmin00@naver.com.
FAU - Chung, Hyo Kyun
AU  - Chung HK
AD  - Research Center for Endocrine and Metabolic Diseases, Chungnam National 
      University School of Medicine, 99, Daehak-ro, Yuseong-gu, 34134, Daejeon, 
      Republic of Korea. Electronic address: hkchung74@cnu.ac.kr.
FAU - Kim, Koon Soon
AU  - Kim KS
AD  - Research Center for Endocrine and Metabolic Diseases, Chungnam National 
      University School of Medicine, 99, Daehak-ro, Yuseong-gu, 34134, Daejeon, 
      Republic of Korea. Electronic address: kunsunkim@cnu.ac.kr.
FAU - Lee, Jae Min
AU  - Lee JM
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Daejeon Eulji Medical Center, Eulji University, 95, Dunsanseo-ro, Seo-gu, 35233 
      Daejeon, Republic of Korea. Electronic address: leejam25@eulji.ac.kr.
FAU - Hong, Jun Hwa
AU  - Hong JH
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Daejeon Eulji Medical Center, Eulji University, 95, Dunsanseo-ro, Seo-gu, 35233 
      Daejeon, Republic of Korea. Electronic address: lammoth@eulji.ac.kr.
FAU - Park, Kang Seo
AU  - Park KS
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Daejeon Eulji Medical Center, Eulji University, 95, Dunsanseo-ro, Seo-gu, 35233 
      Daejeon, Republic of Korea. Electronic address: pkkss@eulji.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170906
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Fatty Acids)
RN  - 0 (Insulin)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Sulfonamides)
RN  - L5IB4XLY36 (udenafil)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/drug effects/*physiology
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Fatty Acids/metabolism
MH  - Insulin/*administration & dosage
MH  - Insulin Resistance/*physiology
MH  - Mice
MH  - Mitochondria/drug effects/*physiology
MH  - Oxygen Consumption/drug effects/*physiology
MH  - Phosphodiesterase 5 Inhibitors/administration & dosage
MH  - Pyrimidines/*administration & dosage
MH  - Sulfonamides/*administration & dosage
OTO - NOTNLM
OT  - Adipocyte
OT  - Insulin sensitivity
OT  - Mitochondrial function
OT  - PDE5 inhibitor
EDAT- 2017/09/11 06:00
MHDA- 2017/10/24 06:00
CRDT- 2017/09/11 06:00
PHST- 2017/08/19 00:00 [received]
PHST- 2017/08/24 00:00 [accepted]
PHST- 2017/09/11 06:00 [pubmed]
PHST- 2017/10/24 06:00 [medline]
PHST- 2017/09/11 06:00 [entrez]
AID - S0006-291X(17)31663-7 [pii]
AID - 10.1016/j.bbrc.2017.08.140 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2017 Nov 4;493(1):631-636. doi: 
      10.1016/j.bbrc.2017.08.140. Epub 2017 Sep 6.