Effects of resistin on insulin signaling in endothelial cells

Zhizhen LI, Fangping LI, Jianhong YE, Li YAN, Zuzhi FU

PDF(114 KB)
PDF(114 KB)
Front. Med. ›› 2009, Vol. 3 ›› Issue (2) : 136-140. DOI: 10.1007/s11684-009-0029-2
RESEARCH ARTICLE

Effects of resistin on insulin signaling in endothelial cells

Author information +
History +

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.

Keywords

resistin / endothelium / nitric oxide / endothelial nitric oxide synthase / Akt-binding protein, mouse

Cite this article

Download citation ▾
Zhizhen LI, Fangping LI, Jianhong YE, Li YAN, Zuzhi FU. Effects of resistin on insulin signaling in endothelial cells. Front Med Chin, 2009, 3(2): 136‒140 https://doi.org/10.1007/s11684-009-0029-2

References

[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
CrossRef Google scholar
[2]
BegumN. Insulin signaling in the vasculature. Front Biosci, 2003, 8: s796-s804
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[18]
PatelS D, RajalaM W, RossettiL, SchererP E, ShapiroL. Disulfide-dependent multimeric assembly of resistin family hormones. Science, 2004, 304(5674): 1154-1158
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar

Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant No. 30570886).

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg
AI Summary AI Mindmap
PDF(114 KB)

Accesses

Citations

Detail

Sections
Recommended

/