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Volume 21, Issue 4
  • ISSN: 1573-3998
  • E-ISSN: 1875-6417

Abstract

Cardiovascular complications are a primary focus in the clinical management of type 2 diabetes, as they are the leading causes of disability and mortality in individuals with diabetes. Insulin resistance and endothelial dysfunction commonly coexist in diabetic patients. An increasing body of research indicates a reciprocal and interconnected association between endothelial function and insulin resistance. Insulin resistance can manifest in two distinct forms: endothelial and metabolic, with the former predominantly affecting vascular endothelial cells and the latter primarily impacting peripheral cells. The understanding of endothelial insulin resistance is crucial in comprehending the pathophysiology of cardiovascular complications in type 2 diabetes. Hence, the objective of this study is to examine the correlations, interplays, and molecular pathways linking endothelial insulin resistance and metabolic insulin resistance, with the aim of offering novel insights and scholarly resources for the prevention and management of diabetic vascular complications.

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2024-11-22

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References

  1. HolmanN. YoungB. GadsbyR. Current prevalence of Type 1 and Type 2 diabetes in adults and children in the UK.Diabet. Med.20153291119112010.1111/dme.1279125962518
     [Google Scholar]
  2. BrunoG. RunzoC. Cavallo-PerinP. MerlettiF. RivettiM. PinachS. NovelliG. TrovatiM. CeruttiF. PaganoG. Incidence of type 1 and type 2 diabetes in adults aged 30-49 years: The population-based registry in the province of Turin, Italy.Diabetes Care200528112613261910.2337/diacare.28.11.261316249528
     [Google Scholar]
  3. ZhengY. LeyS.H. HuF.B. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications.Nat. Rev. Endocrinol.2018142889810.1038/nrendo.2017.15129219149
     [Google Scholar]
  4. CersosimoE. DeFronzoR.A. Insulin resistance and endothelial dysfunction: The road map to cardiovascular diseases.Diabetes Metab. Res. Rev.200622642343610.1002/dmrr.63416506274
     [Google Scholar]
  5. KubotaT. KubotaN. KumagaiH. YamaguchiS. KozonoH. TakahashiT. InoueM. ItohS. TakamotoI. SasakoT. KumagaiK. KawaiT. HashimotoS. KobayashiT. SatoM. TokuyamaK. NishimuraS. TsunodaM. IdeT. MurakamiK. YamazakiT. EzakiO. KawamuraK. MasudaH. MoroiM. SugiK. OikeY. ShimokawaH. YanagiharaN. TsutsuiM. TerauchiY. TobeK. NagaiR. KamataK. InoueK. KodamaT. UekiK. KadowakiT. Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle.Cell Metab.201113329430710.1016/j.cmet.2011.01.01821356519
     [Google Scholar]
  6. BoucherJ. KleinriddersA. KahnC.R. Insulin receptor signaling in normal and insulin-resistant states.Cold Spring Harb. Perspect. Biol.201461a00919110.1101/cshperspect.a00919124384568
     [Google Scholar]
  7. MontagnaniM. ChenH. BarrV.A. QuonM.J. Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser(1179).J. Biol. Chem.200127632303923039810.1074/jbc.M10370220011402048
     [Google Scholar]
  8. EscuderoC.A. HerlitzK. TroncosoF. GuevaraK. AcurioJ. AguayoC. GodoyA.S. GonzálezM. Pro-angiogenic role of insulin: From physiology to pathology.Front. Physiol.2017820410.3389/fphys.2017.0020428424632
     [Google Scholar]
  9. Rask-MadsenC. BuonomoE. LiQ. ParkK. ClermontA.C. YerokunO. RekhterM. KingG.L. Hyperinsulinemia does not change atherosclerosis development in apolipoprotein E null mice.Arterioscler. Thromb. Vasc. Biol.20123251124113110.1161/ATVBAHA.111.23955822426129
     [Google Scholar]
  10. Rask-MadsenC. LiQ. FreundB. FeatherD. AbramovR. WuI.H. ChenK. HiraokaY.J. GoldenbogenJ. SotiropoulosK.B. ClermontA. GeraldesP. Dall’OssoC. WagersA.J. HuangP.L. RekhterM. ScaliaR. KahnC.R. KingG.L. Loss of insulin signaling in vascular endothelial cells accelerates atherosclerosis in apolipoprotein E null mice.Cell Metab.201011537938910.1016/j.cmet.2010.03.01320444418
     [Google Scholar]
  11. MontagnaniM. GolovchenkoI. KimI. KohG.Y. GoalstoneM.L. MundhekarA.N. JohansenM. KucikD.F. QuonM.J. DrazninB. Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells.J. Biol. Chem.200227731794179910.1074/jbc.M10372820011707433
     [Google Scholar]
  12. KingG.L. ParkK. LiQ. Selective insulin resistance and the development of cardiovascular diseases in diabetes: The 2015 edwin bierman award lecture.Diabetes20166561462147110.2337/db16‑015227222390
     [Google Scholar]
  13. FeenerE.P. KingG.L. Endothelial dysfunction in diabetes mellitus: Role in cardiovascular disease.Heart Fail Monit2001137482
     [Google Scholar]
  14. HsuehW.A. LyonC.J. QuiñonesM.J. Insulin resistance and the endothelium.Am. J. Med.2004117210911710.1016/j.amjmed.2004.02.04215234647
     [Google Scholar]
  15. MuniyappaR. SowersJ.R. Role of insulin resistance in endothelial dysfunction.Rev. Endocr. Metab. Disord.201314151210.1007/s11154‑012‑9229‑123306778
     [Google Scholar]
  16. KimJ. MontagnaniM. KohK.K. QuonM.J. Reciprocal relationships between insulin resistance and endothelial dysfunction: Molecular and pathophysiological mechanisms.Circulation2006113151888190410.1161/CIRCULATIONAHA.105.56321316618833
     [Google Scholar]
  17. HuangP.L. eNOS, metabolic syndrome and cardiovascular disease.Trends Endocrinol. Metab.200920629530210.1016/j.tem.2009.03.00519647446
     [Google Scholar]
  18. MuniyappaR. ChenH. MontagnaniM. ShermanA. QuonM.J. Endothelial dysfunction due to selective insulin resistance in vascular endothelium: Insights from mechanistic modeling.Am. J. Physiol. Endocrinol. Metab.20203193E629E64610.1152/ajpendo.00247.202032776829
     [Google Scholar]
  19. JiangZ.Y. LinY.W. ClemontA. FeenerE.P. HeinK.D. IgarashiM. YamauchiT. WhiteM.F. KingG.L. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats.J. Clin. Invest.1999104444745710.1172/JCI597110449437
     [Google Scholar]
  20. CaballeroA.E. Endothelial dysfunction, inflammation, and insulin resistance: A focus on subjects at risk for type 2 diabetes.Curr. Diab. Rep.20044423724610.1007/s11892‑004‑0074‑915265464
     [Google Scholar]
  21. PetrieJ.R. GuzikT.J. TouyzR.M. Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms.Can. J. Cardiol.201834557558410.1016/j.cjca.2017.12.00529459239
     [Google Scholar]
  22. CookeJ.P. Flow, NO, and atherogenesis.Proc. Natl. Acad. Sci.2003100376877010.1073/pnas.043008210012552094
     [Google Scholar]
  23. SteinbergH.O. BrechtelG. JohnsonA. FinebergN. BaronA.D. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release.J. Clin. Invest.19949431172117910.1172/JCI1174338083357
     [Google Scholar]
  24. IsenovicE.R. DivaldA. MilivojevicN. GrgurevicT. FisherS.E. SowersJ.R. Interactive effects of insulin-like growth factor-1 and β-estradiol on endothelial nitric oxide synthase activity in rat aortic endothelial cells.Metabolism200352448248710.1053/meta.2003.5007912701063
     [Google Scholar]
  25. MuniyappaR. SowersJ.R. Endothelial insulin and IGF-1 receptors: When yes means NO.Diabetes20126192225222710.2337/db12‑065422923650
     [Google Scholar]
  26. HillM.A. YangY. ZhangL. SunZ. JiaG. ParrishA.R. SowersJ.R. Insulin resistance, cardiovascular stiffening and cardiovascular disease.Metabolism202111915476610.1016/j.metabol.2021.15476633766485
     [Google Scholar]
  27. CongerJ.D. Endothelial regulation of vascular tone.Hosp. Pract.19942910117126, 125-12610.1080/21548331.1994.114430957929667
     [Google Scholar]
  28. BaronA.D. TarshobyM. HookG. LazaridisE.N. CroninJ. JohnsonA. SteinbergH.O. Interaction between insulin sensitivity and muscle perfusion on glucose uptake in human skeletal muscle: Evidence for capillary recruitment.Diabetes200049576877410.2337/diabetes.49.5.76810905485
     [Google Scholar]
  29. TaguchiK. HidaM. HasegawaM. NarimatsuH. MatsumotoT. KobayashiT. Suppression of GRK2 expression reduces endothelial dysfunction by restoring glucose homeostasis.Sci. Rep.201771843610.1038/s41598‑017‑08998‑528814745
     [Google Scholar]
  30. SteinbergH.O. ParadisiG. HookG. CrowderK. CroninJ. BaronA.D. Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production.Diabetes20004971231123810.2337/diabetes.49.7.123110909983
     [Google Scholar]
  31. TsutsuiM. TanimotoA. TamuraM. MukaeH. YanagiharaN. ShimokawaH. OtsujiY. Significance of nitric oxide synthases: Lessons from triple nitric oxide synthases null mice.J. Pharmacol. Sci.20151271425210.1016/j.jphs.2014.10.00225704017
     [Google Scholar]
  32. TookeJ. The association between insulin resistance and endotheliopathy.Diabetes Obes. Metab.19991S1172210.1046/j.1463‑1326.1999.0010s1017.x11220284
     [Google Scholar]
  33. QuiñonesM.J. NicholasS.B. LyonC.J. Insulin resistance and the endothelium.Curr. Diab. Rep.20055424625310.1007/s11892‑005‑0018‑z16033673
     [Google Scholar]
  34. SaltielA.R. KahnC.R. Insulin signalling and the regulation of glucose and lipid metabolism.Nature2001414686579980610.1038/414799a11742412
     [Google Scholar]
  35. DimmelerS. FlemingI. FisslthalerB. HermannC. BusseR. ZeiherA.M. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation.Nature1999399673660160510.1038/2122410376603
     [Google Scholar]
  36. ZengG. NystromF.H. RavichandranL.V. CongL.N. KirbyM. MostowskiH. QuonM.J. Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells.Circulation2000101131539154510.1161/01.CIR.101.13.153910747347
     [Google Scholar]
  37. KahnC.R. Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes.Diabetes19944381066108510.2337/diab.43.8.10668039601
     [Google Scholar]
  38. OhkitaM. TawaM. KitadaK. MatsumuraY. Pathophysiological roles of endothelin receptors in cardiovascular diseases.J. Pharmacol. Sci.2012119430231310.1254/jphs.12R01CR22863667
     [Google Scholar]
  39. XuJ. ZouM.H. Molecular insights and therapeutic targets for diabetic endothelial dysfunction.Circulation2009120131266128610.1161/CIRCULATIONAHA.108.83522319786641
     [Google Scholar]
  40. MuniyappaR. MontagnaniM. KohK.K. QuonM.J. Cardiovascular actions of insulin.Endocr. Rev.200728546349110.1210/er.2007‑000617525361
     [Google Scholar]
  41. SáezT. ToledoF. SobreviaL. Extracellular vesicles and insulin resistance: A potential interaction in vascular dysfunction.Curr. Vasc. Pharmacol.201917549149710.2174/157016111666618100209574530277159
     [Google Scholar]
  42. ZhouZ. ColladoA. SunC. TratsiakovichY. MahdiA. WinterH. ChernogubovaE. SeimeT. NarayananS. JiaoT. JinH. AlvarssonM. ZhengX. YangJ. HedinU. CatrinaS.B. MaegdefesselL. PernowJ. Downregulation of erythrocyte miR-210 induces endothelial dysfunction in type 2 diabetes.Diabetes202271228529710.2337/db21‑009334753800
     [Google Scholar]
  43. XiongY. ChenL. YanC. ZhouW. EndoY. LiuJ. HuL. HuY. MiB. LiuG. Circulating exosomal miR‐20b‐5p inhibition restores wnt9b signaling and reverses diabetes‐associated impaired wound healing.Small2020163190404410.1002/smll.20190404431867895
     [Google Scholar]
  44. XiaoX. XuM. YuH. WangL. LiX. RakJ. WangS. ZhaoR.C. Mesenchymal stem cell-derived small extracellular vesicles mitigate oxidative stress-induced senescence in endothelial cells via regulation of miR-146a/Src.Signal Transduct. Target. Ther.20216135410.1038/s41392‑021‑00765‑334675187
     [Google Scholar]
  45. AbdelsaidK. SudhaharV. HarrisR.A. DasA. YounS.W. LiuY. McMenaminM. HouY. FultonD. HamrickM.W. TangY. FukaiT. FukaiU.M. Exercise improves angiogenic function of circulating exosomes in type 2 diabetes: Role of exosomal SOD3.FASEB J.2022363e2217710.1096/fj.202101323R35142393
     [Google Scholar]
  46. SchinzariF. CardilloC. Intricacies of the endothelin system in human obesity: role in the development of complications and potential as a therapeutic target.Can. J. Physiol. Pharmacol.202098956356910.1139/cjpp‑2019‑065132808824
     [Google Scholar]
  47. SekiT. HosakaK. FischerC. LimS. AnderssonP. AbeM. IwamotoH. GaoY. WangX. FongG.H. CaoY. Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning.J. Exp. Med.2018215261162610.1084/jem.2017101229305395
     [Google Scholar]
  48. YouM. LiuY. WangB. LiL. ZhangH. HeH. ZhouQ. CaoT. WangL. ZhaoZ. ZhuZ. GaoP. YanZ. Asprosin induces vascular endothelial-to-mesenchymal transition in diabetic lower extremity peripheral artery disease.Cardiovasc. Diabetol.20222112510.1186/s12933‑022‑01457‑035168605
     [Google Scholar]
  49. HanX. WuY. LiuX. MaL. LvT. SunQ. XuW. ZhangS. WangK. WangW. MaX. LiuH. Adiponectin improves coronary no-reflow injury by protecting the endothelium in rats with type 2 diabetes mellitus.Biosci. Rep.2017374BSR2017028210.1042/BSR2017028228667102
     [Google Scholar]
  50. InoguchiT. UmedaF. WatanabeJ. IbayashiH. Reduced serum-stimulatory activity on prostacyclin production by cultured aortic endothelial cells in diabetes mellitus.Pathophysiol. Haemost. Thromb.198616644745210.1159/0002153233556348
     [Google Scholar]
  51. TsujiM. TakahashiT. Evaluation of plasma 6-keto-prostaglandin F1 alpha and thromboxane B2 in diabetic neuropathy.Endocrin. J.1987631263310.1507/endocrine1927.63.1_263556671
     [Google Scholar]
  52. MareiI. ChidiacO. ThomasB. PasquierJ. DarghamS. RobayA. VakayilM. JameeshM. TriggleC. RafiiA. JayyousiA. Al SuwaidiJ. Abi KhalilC. Angiogenic content of microparticles in patients with diabetes and coronary artery disease predicts networks of endothelial dysfunction.Cardiovasc. Diabetol.20222111710.1186/s12933‑022‑01449‑035109843
     [Google Scholar]
  53. WangX.L. ZhangW. LiZ. HanW.Q. WuH.Y. WangQ.R. LiuX.H. XingK. ChengG. ChangF.J. Vascular damage effect of circulating microparticles in patients with ACS is aggravated by type 2 diabetes.Mol. Med. Rep.202123647410.3892/mmr.2021.1211333899122
     [Google Scholar]
  54. HirotaT. LevyJ.H. IbaT. The influence of hyperglycemia on neutrophil extracellular trap formation and endothelial glycocalyx damage in a mouse model of type 2 diabetes.Microcirculation2020275e1261710.1111/micc.1261732125048
     [Google Scholar]
  55. ZengM. LuoY. XuC. LiR. ChenN. DengX. FangD. WangL. WuJ. LuoM. Platelet-endothelial cell interactions modulate smooth muscle cell phenotype in an in vitro model of type 2 diabetes mellitus.Am. J. Physiol. Cell Physiol.20193162C186C19710.1152/ajpcell.00428.201830517030
     [Google Scholar]
  56. YuL. LiangQ. ZhangW. LiaoM. WenM. ZhanB. BaoH. ChengX. HSP22 suppresses diabetes-induced endothelial injury by inhibiting mitochondrial reactive oxygen species formation.Redox Biol.20192110109510.1016/j.redox.2018.10109530640127
     [Google Scholar]
  57. MaqboolA. WattN.T. HaywoodN. ViswambharanH. SkromnaA. MakavaN. VisnagriA. ShawerH.M. BridgeK. MuminovS.K. GriffinK. BeechD.J. WheatcroftS.B. PorterK.E. SimmonsK.J. SukumarP. ShahA.M. CubbonR.M. KearneyM.T. YuldashevaN.Y. Divergent effects of genetic and pharmacological inhibition of Nox2 NADPH oxidase on insulin resistance-related vascular damage.Am. J. Physiol. Cell Physiol.20203191C64C7410.1152/ajpcell.00389.201932401607
     [Google Scholar]
  58. LeeJ.Y. LeeY.J. JeonH.Y. HanE.T. ParkW.S. HongS.H. KimY.M. HaK.S. The vicious cycle between transglutaminase 2 and reactive oxygen species in hyperglycemic memory–induced endothelial dysfunction.FASEB J.20193311126551266710.1096/fj.201901358RR31462079
     [Google Scholar]
  59. ViswambharanH. YuldashevaN.Y. ImrieH. BridgeK. HaywoodN.J. SkromnaA. HemmingsK.E. ClarkE.R. GatenbyV.K. CordellP. SimmonsK.J. MakavaN. AbudushalamuY. EndeshN. BrownJ. WalkerA.M.N. FutersS.T. PorterK.E. CubbonR.M. NaseemK. ShahA.M. BeechD.J. WheatcroftS.B. KearneyM.T. SukumarP. Novel paracrine action of endothelium enhances glucose uptake in muscle and fat.Circ. Res.2021129772073410.1161/CIRCRESAHA.121.31951734420367
     [Google Scholar]
  60. MahdiA. TengbomJ. AlvarssonM. WernlyB. ZhouZ. PernowJ. Red blood cell peroxynitrite causes endothelial dysfunction in type 2 diabetes mellitus via arginase.Cells202097171210.3390/cells907171232708826
     [Google Scholar]
  61. ZhouZ. MahdiA. TratsiakovichY. ZahoránS. KövameesO. NordinF. Uribe GonzalezA.E. AlvarssonM. ÖstensonC.G. AnderssonD.C. HedinU. HermeszE. LundbergJ.O. YangJ. PernowJ. Erythrocytes from patients with type 2 diabetes induce endothelial dysfunction via arginase I.J. Am. Coll. Cardiol.201872776978010.1016/j.jacc.2018.05.05230092954
     [Google Scholar]
  62. CostantinoS. PaneniF. BattistaR. CastelloL. CaprettiG. ChiandottoS. TaneseL. RussoG. PitoccoD. LanzaG.A. VolpeM. LüscherT.F. CosentinoF. Impact of glycemic variability on chromatin remodeling, oxidative stress, and endothelial dysfunction in patients with type 2 diabetes and with target HbA1c levels.Diabetes20176692472248210.2337/db17‑029428634176
     [Google Scholar]
  63. Berra-RomaniB.R. SilvaG.A. GuadarramaV.A. AlonsoF.J.C. RomeroA.J. TreviñoS. GómezS.J. SantiagoC.N. CarrascoG.M. MocciaF. Type 2 diabetes alters intracellular Ca2+ handling in native endothelium of excised rat aorta.Int. J. Mol. Sci.201921125010.3390/ijms2101025031905880
     [Google Scholar]
  64. MooreM.C. CherringtonA.D. ClineG. PagliassottiM.J. JonesE.M. NealD.W. BadetC. ShulmanG.I. Sources of carbon for hepatic glycogen synthesis in the conscious dog.J. Clin. Invest.199188257858710.1172/JCI1153421864968
     [Google Scholar]
  65. LetoD. SaltielA.R. Regulation of glucose transport by insulin: Traffic control of GLUT4.Nat. Rev. Mol. Cell Biol.201213638339610.1038/nrm335122617471
     [Google Scholar]
  66. CrossD.A.E. AlessiD.R. CohenP. AndjelkovichM. HemmingsB.A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.Nature1995378655978578910.1038/378785a08524413
     [Google Scholar]
  67. NewgardC.B. BradyM.J. O’DohertyR.M. SaltielA.R. Organizing glucose disposal: Emerging roles of the glycogen targeting subunits of protein phosphatase-1.Diabetes200049121967197710.2337/diabetes.49.12.196711117996
     [Google Scholar]
  68. AgiusL. Role of glycogen phosphorylase in liver glycogen metabolism.Mol. Aspects Med.201546344510.1016/j.mam.2015.09.00226519772
     [Google Scholar]
  69. DongX.C. CoppsK.D. GuoS. LiY. KolliparaR. DePinhoR.A. WhiteM.F. Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation.Cell Metab.200881657610.1016/j.cmet.2008.06.00618590693
     [Google Scholar]
  70. RobertsC.K. HevenerA.L. BarnardR.J. Metabolic syndrome and insulin resistance: Underlying causes and modification by exercise training.Compr. Physiol.20133115810.1002/cphy.c11006223720280
     [Google Scholar]
  71. RebrinK. SteilG.M. MittelmanS.D. BergmanR.N. Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs.J. Clin. Invest.199698374174910.1172/JCI1188468698866
     [Google Scholar]
  72. KerstenS. Mechanisms of nutritional and hormonal regulation of lipogenesis.EMBO Rep.20012428228610.1093/embo‑reports/kve07111306547
     [Google Scholar]
  73. LeeS.H. ParkS.Y. ChoiC.S. Insulin resistance: From mechanisms to therapeutic strategies.Diabetes Metab. J.2022461153710.4093/dmj.2021.028034965646
     [Google Scholar]
  74. AielloL.P. CahillM.T. WongJ.S. Systemic considerations in the management of diabetic retinopathy.Am. J. Ophthalmol.2001132576077610.1016/S0002‑9394(01)01124‑211704039
     [Google Scholar]
  75. RodenM. StinglH. ChandramouliV. SchumannW.C. HoferA. LandauB.R. NowotnyP. WaldhäuslW. ShulmanG.I. Effects of free fatty acid elevation on postabsorptive endogenous glucose production and gluconeogenesis in humans.Diabetes200049570170710.2337/diabetes.49.5.70110905476
     [Google Scholar]
  76. PerseghinG. GhoshS. GerowK. ShulmanG.I. Metabolic defects in lean nondiabetic offspring of NIDDM parents: A cross-sectional study.Diabetes19974661001100910.2337/diab.46.6.10019166672
     [Google Scholar]
  77. KojtaI. ChacińskaM. ZabielskaB.A. Obesity, bioactive lipids, and adipose tissue inflammation in insulin resistance.Nutrients2020125130510.3390/nu1205130532375231
     [Google Scholar]
  78. OlefskyJ.M. GlassC.K. Macrophages, inflammation, and insulin resistance.Annu. Rev. Physiol.201072121924610.1146/annurev‑physiol‑021909‑13584620148674
     [Google Scholar]
  79. DandonaP. GhanimH. ChaudhuriA. DhindsaS. KimS.S. Macronutrient intake induces oxidative and inflammatory stress: Potential relevance to atherosclerosis and insulin resistance.Exp. Mol. Med.201042424525310.3858/emm.2010.42.4.03320200475
     [Google Scholar]
  80. TantiJ.F. CeppoF. JagerJ. BerthouF. Implication of inflammatory signaling pathways in obesity-induced insulin resistance.Front. Endocrinol.2013318110.3389/fendo.2012.0018123316186
     [Google Scholar]
  81. LoveK.M. BarrettE.J. MalinS.K. ReuschJ.E.B. RegensteinerJ.G. LiuZ. Diabetes pathogenesis and management: The endothelium comes of age.J. Mol. Cell Biol.202113750051210.1093/jmcb/mjab02433787922
     [Google Scholar]
  82. SudhaharV. OkurM.N. BagiZ. O’BryanJ.P. HayN. MakinoA. PatelV.S. PhillipsS.A. SteppD. Ushio-FukaiM. FukaiT. Akt2 (Protein Kinase B Beta) stabilizes ATP7A, a copper transporter for extracellular superoxide dismutase, in vascular smooth muscle.Arterioscler. Thromb. Vasc. Biol.201838352954110.1161/ATVBAHA.117.30981929301787
     [Google Scholar]
  83. GuoZ. ZhangY. LiuC. YounJ.Y. CaiH. Toll-like receptor 2 (TLR2) knockout abrogates diabetic and obese phenotypes while restoring endothelial function via inhibition of NOX1.Diabetes20217092107211910.2337/db20‑059134127487
     [Google Scholar]
  84. MaoH. LiL. FanQ. AngeliniA. SahaP.K. WuH. BallantyneC.M. HartigS.M. XieL. PiX. Loss of bone morphogenetic protein-binding endothelial regulator causes insulin resistance.Nat. Commun.2021121192710.1038/s41467‑021‑22130‑233772019
     [Google Scholar]
  85. LiX. JinS.J. SuJ. LiX.X. XuM. Acid sphingomyelinase down‐regulation alleviates vascular endothelial insulin resistance in diabetic rats.Basic Clin. Pharmacol. Toxicol.2018123664565910.1111/bcpt.1307329923306
     [Google Scholar]
  86. RehmanK. HaiderK. JabeenK. AkashM.S.H. Current perspectives of oleic acid: Regulation of molecular pathways in mitochondrial and endothelial functioning against insulin resistance and diabetes.Rev. Endocr. Metab. Disord.202021463164310.1007/s11154‑020‑09549‑632125563
     [Google Scholar]
  87. MartinC.L.N. JúniorG.L.T. FernandesL.A.B. CesarinoC.B. NakazoneM.A. MachadoM.N. ToledoY.J.C. MartinV.J.F. Effect of vildagliptin versus glibenclamide on endothelial function and arterial stiffness in patients with type 2 diabetes and hypertension: A randomized controlled trial.Acta Diabetol.201855121237124510.1007/s00592‑018‑1204‑130094725
     [Google Scholar]
  88. LiQ. LinY. WangS. ZhangL. GuoL. GLP-1 inhibits high-glucose-induced oxidative injury of vascular endothelial cells.Sci. Rep.201771800810.1038/s41598‑017‑06712‑z28808291
     [Google Scholar]
  89. BasuA. CharkoudianN. SchrageW. RizzaR.A. BasuR. JoynerM.J. Beneficial effects of GLP-1 on endothelial function in humans: dampening by glyburide but not by glimepiride.Am. J. Physiol. Endocrinol. Metab.20072935E1289E129510.1152/ajpendo.00373.200717711996
     [Google Scholar]
  90. WangZ.J. ChangL.L. WuJ. PanH.M. ZhangQ.Y. WangM.J. XinX.M. LuoS.S. ChenJ.A. GuX.F. GuoW. ZhuY.Z. A novel rhynchophylline analog, Y396, inhibits endothelial dysfunction induced by oxidative stress in diabetes through epidermal growth factor receptor.Antioxid. Redox Signal.2020321174376510.1089/ars.2018.772131892280
     [Google Scholar]
  91. LiuF. FangS. LiuX. LiJ. WangX. CuiJ. ChenT. LiZ. YangF. TianJ. LiH. YinL. YuB. Omentin-1 protects against high glucose-induced endothelial dysfunction via the AMPK/PPARδ signaling pathway.Biochem. Pharmacol.202017411383010.1016/j.bcp.2020.11383032001235
     [Google Scholar]
  92. YingL. LiN. HeZ. ZengX. NanY. ChenJ. MiaoP. YingY. LinW. ZhaoX. LuL. ChenM. CenW. GuoT. LiX. HuangZ. WangY. Fibroblast growth factor 21 Ameliorates diabetes-induced endothelial dysfunction in mouse aorta via activation of the CaMKK2/AMPKα signaling pathway.Cell Death Dis.201910966510.1038/s41419‑019‑1893‑631511499
     [Google Scholar]
  93. AliM. MaliV. HaddoxS. AbdelGhanyS.M. El-deekS.E.M. AbulfadlA. MatrouguiK. BelmadaniS. Essential role of IL-12 in angiogenesis in type 2 diabetes.Am. J. Pathol.2017187112590260110.1016/j.ajpath.2017.07.02128837799
     [Google Scholar]
/content/journals/cdr/10.2174/0115733998288601240327065724
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Endothelial versus Metabolic Insulin Resistance, A Descriptive Review
Curr. Diabetes Rev. 21, E050424228674 (2025); https://doi.org/10.2174/0115733998288601240327065724
/content/journals/cdr/10.2174/0115733998288601240327065724
/content/journals/cdr/10.2174/0115733998288601240327065724
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  • Article Type:     Review Article
Keyword(s): diabetes-related cardiovascular complications; endothelial dysfunction; endothelial insulin resistance; metabolic insulin resistance; oxidative stress; therapies

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