RESEARCH ARTICLE

Effects of resistin on insulin signaling in endothelial cells

  • Zhizhen LI 1 ,
  • Fangping LI 2 ,
  • Jianhong YE 2 ,
  • Li YAN 2 ,
  • Zuzhi FU , 2
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  • 1. Department of Endocrinology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China
  • 2. Department of Endocrinology, Second Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, China

Received date: 20 Dec 2008

Accepted date: 17 Jan 2009

Published date: 05 Jun 2009

Copyright

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

The objective of this study was to investigate the effects of resistin on insulin signaling in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with recombinant human resistin (0-100 ng/mL) for 24 h. Akt and endothelial nitric oxide synthase (eNOS) phosphorylation levels of endothelial cells under basal or insulin stimulated conditions were measured by Western blot. Nitric oxide (NO) production of HUVECs was also detected. The results showed that resistin could significantly inhibit Akt and eNOS phosphorylation and NO production in endothelial cells under insulin stimulated conditions (P< 0.05 vs control). But under basal conditions, treatment with resistin could result in a decrease in eNOS phosphorylation (P< 0.05 vs control) but had no effect on NO production and Akt phosphorylation levels. These findings suggested that resistin exerted an inhibitory effect on NO production by inhibiting insulin signaling and eNOS phosphorylation in endothelial cells.

Cite this article

Zhizhen LI , Fangping LI , Jianhong YE , Li YAN , Zuzhi FU . Effects of resistin on insulin signaling in endothelial cells[J]. Frontiers of Medicine, 2009 , 3(2) : 136 -140 . DOI: 10.1007/s11684-009-0029-2

Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant No. 30570886).
1
GrundyS M, BrewerH B Jr, CleemanJ I, SmithS C Jr, LenfantC. American Heart Association; National Heart, Lung, and Blood Institute. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation, 2004, 109(3): 433-438

DOI

2
BegumN. Insulin signaling in the vasculature. Front Biosci, 2003, 8: s796-s804

DOI

3
WellenK E, HotamisligilG S. Inflammation, stress, and diabetes. J Clin Invest, 2005, 115(5): 1111-1119

4
SteppanC M, BaileyS T, BhatS, BrownE J, BanerjeeR R, WrightC M, PatelH R, AhimaR S, LazarM A. The hormone resistin links obesity to diabetes. Nature, 2001, 409(6818): 307-312

DOI

5
SteppanC M, BrownE J, WrightC M, BhatS, BanerjeeR R, DaiC Y, EndersG H, SilbergD G, WenX, WuG D, LazarM A. A family of tissue-specific resistin-like molecules. Proc Natl Acad Sci U S A, 2001, 98(2): 502-506

DOI

6
PatelL, BuckelsA C, KinghornI J, MurdockP R, HolbrookJ D, PlumptonC, MacpheeC H, SmithS A. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun, 2003, 300(2): 472-476

DOI

7
KaserS, KaserA, SandhoferA, EbenbichlerC F, TilgH, PatschJ R. Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro. Biochem Biophys Res Commun, 2003, 309(2): 286-290

DOI

8
BokarewaM, NagaevI, DahlbergL, SmithU, TarkowskiA. Resistin, an adipokine with potent proinflammatory properties. J Immunol, 2005, 174(9): 5789-5795

9
MinterA J, DawesJ, ChestermanC N. Effects of heparin and endothelial cell growth supplement on haemostatic functions of vascular endothelium. Thromb Haemost, 1992, 67(6): 718-723

10
HingoraniA D, CrossJ, KharbandaR K, MullenM J, BhagatK, TaylorM, DonaldA E, PalaciosM, GriffinG E, DeanfieldJ E, MacAllisterR J, VallanceP. Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation, 2000, 102(9): 994-999

11
BhagatK, VallanceP. Inflammatory cytokines impair endothelium-dependent dilatation in human veins in vivo. Circulation, 1997, 96(9): 3042-3047

12
ReillyM P, LehrkeM, WolfeM L, RohatgiA, LazarM A, RaderD J. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation, 2005, 111(7): 932-939

DOI

13
ShenY H, ZhangL, GanY, WangX, WangJ, LeMaireS A, CoselliJ S, WangX L. Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) mediates p38 MAPK stress signal-induced inhibition of insulin signaling. A cross-talk between stress signaling and insulin signaling in resistin-treated human endothelial cells. J Biol Chem, 2006, 281(12): 7727-7736

DOI

14
VermaS, LiS H, WangC H, FedakP W, LiR K, WeiselR D, MickleD A. Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation, 2003, 108(6): 736-740

DOI

15
KawanamiD, MaemuraK, TakedaN, HaradaT, NojiriT, ImaiY, ManabeI, UtsunomiyaK, NagaiR. Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem Biophys Res Commun, 2004, 314(2): 415-419

DOI

16
CalabroP, SamudioI, WillersonJ T, YehE T. Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways. Circulation, 2004, 110(21): 3335-3340

DOI

17
GraveleauC, ZahaV G, MohajerA, BanerjeeR R, Dudley-RuckerN, SteppanC M, RajalaM W, SchererP E, AhimaR S, LazarM A, AbelE D. Mouse and human resistins impair glucose transport in primary mouse cardiomyocytes, and oligomerization is required for this biological action. J Biol Chem, 2005, 280(36): 31679-31685

DOI

18
PatelS D, RajalaM W, RossettiL, SchererP E, ShapiroL. Disulfide-dependent multimeric assembly of resistin family hormones. Science, 2004, 304(5674): 1154-1158

DOI

19
WyattA W, SteinertJ R, Wheeler-JonesC P, MorganA J, SugdenD, PearsonJ D, SobreviaL, MannG E. Early activation of the p42/p44MAPK pathway mediates adenosine-induced nitric oxide production in human endothelial cells: a novel calcium-insensitive mechanism. FASEB J, 2002, 16(12): 1584-1594

DOI

20
MorrowV A, FoufelleF, ConnellJ M, PetrieJ R, GouldG W, SaltI P. Direct activation of AMP-activated protein kinase stimulates nitric-oxide synthesis in human aortic endothelial cells. J Biol Chem, 2003, 278(34): 31629-31639

DOI

21
SatohH, NguyenM T, MilesP D, ImamuraT, UsuiI, OlefskyJ M. Adenovirus-mediated chronic “hyper-resistinemia” leads to in vivo insulin resistance in normal rats. J Clin Invest, 2004, 114(2): 224-231

22
KitagawaY, BujoH, TakahashiK, ShibasakiM, IshikawaK, YaguiK, HashimotoN, NodaK, NakamuraT, YanoS, SaitoY. Impaired glucose tolerance is accompanied by decreased insulin sensitivity in tissues of mice implanted with cells that overexpress resistin. Diabetologia, 2004, 47(10): 1847-1853

DOI

23
RangwalaS M, RichA S, RhoadesB, ShapiroJ S, ObiciS, RossettiL, LazarM A. Abnormal glucose homeostasis due to chronic hyperresistinemia. Diabetes, 2004, 53(8): 1937-1941

DOI

24
MoonB, KwanJ J, DuddyN, SweeneyG, BegumN. Resistin inhibits glucose uptake in L6 cells independently of changes in insulin signaling and GLUT4 translocation. Am J Physiol Endocrinol Metab, 2003, 285(1): E106-E115

25
MuseE D, ObiciS, BhanotS, MoniaB P, McKayR A, RajalaM W, SchererP E, RossettiL. Role of resistin in diet-induced hepatic insulin resistance. J Clin Invest, 2004, 114(2): 232-239

26
FehmannH C, HeynJ. Plasma resistin levels in patients with type 1 and type 2 diabetes mellitus and in healthy controls. Horm Metab Res, 2002, 34(11,12): 671-673

27
BurnettM S, LeeC W, KinnairdT D, StabileE, DurraniS, DullumM K, DevaneyJ M, FishmanC, StamouS, CanosD, ZbindenS, ClavijoL C, JangG J, AndrewsJ A, ZhuJ, EpsteinS E. The potential role of resistin in atherogenesis. Atherosclerosis, 2005, 182(2): 241-248

DOI

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