Skip to content
2000
Volume 20, Issue 2
  • ISSN: 1574-3624
  • E-ISSN: 2212-389X

Abstract

Parkinson’s Disease (PD) is a common neurodegenerative disease, characterized by motor deficit. Diabetes Mellitus (DM) is a metabolic condition characterized by high glucose levels in the blood. The prevalence of chronic disorders like PD has significantly risen in recent decades. Emerging research has increasingly linked PD with Type 2 Diabetes Mellitus (T2DM) in recent years. Apart from the β-cells of the pancreas, insulin is secreted by the choroid plexus in the human brain which is essential for neuroprotection which regulates neurogenesis, oxidative stress, synaptic plasticity, neuronal survival, and neuro-inflammation. The abnormalities in the insulin signaling pathway may be responsible for neurodegeneration insulin dysregulation, from the aggregation of α-synuclein, neuroinflammation, mitochondrial dysfunction, and altered synaptic plasticity. DM or Insulin resistance is considered a risk factor for the development of PD. Due to the lack of treatment options for PD, consistent research is going on to find a potential drug as a treatment option for PD, and due to its molecular links, the antidiabetic drugs are considered as potential candidates for PD. This review will discuss the potential cellular mechanisms shared between T2DM and PD as well as the role of antidiabetics in this disease and clinical manifestations such as its severity and prognosis.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cst/10.2174/0115743624334102241115162404
2024-11-19
2025-09-18

  • From This Site

    /content/journals/cst/10.2174/0115743624334102241115162404
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. TysnesO.B. StorsteinA. Epidemiology of Parkinson’s disease.J. Neural Transm. (Vienna)2017124890190510.1007/s00702‑017‑1686‑y28150045
     [Google Scholar]
  2. XiongY. YuJ. Modeling Parkinson’s disease in Drosophila: What have we learned for dominant traits?Front. Neurol.2018922810.3389/fneur.2018.0022829686647
     [Google Scholar]
  3. AthaudaD. FoltynieT. Insulin resistance and Parkinson’s disease: A new target for disease modification?Prog. Neurobiol.2016145-1469812010.1016/j.pneurobio.2016.10.00127713036
     [Google Scholar]
  4. Jose SanzF. Solana-ManriqueC. Lilao-GarzónJ. Brito-CasillasY. Muñoz-DescalzoS. Exploring the link between Parkinson’s disease and diabetes mellitus in Drosophila.bioRxiv202210.1101/2022.02.18.481049
     [Google Scholar]
  5. American Diabetes AssociationDiagnosis and classification of diabetes mellitus.Diabetes Care201336Suppl 1S67S7410.2337/dc13‑S06723390628
     [Google Scholar]
  6. HassanA. Sharma KandelR. MishraR. GautamJ. AlarefA. JahanN. Diabetes mellitus and Parkinson’s disease: Shared pathophysiological links and possible therapeutic implications.Cureus2020128e985310.7759/cureus.985332832307
     [Google Scholar]
  7. YueX. LiH. YanH. ZhangP. ChangL. LiT. Risk of Parkinson disease in diabetes mellitus.Medicine (Baltimore)20169518e354910.1097/MD.000000000000354927149468
     [Google Scholar]
  8. RenaudJ. BassareoV. BeaulieuJ. PinnaA. SchlichM. LavoieC. MurtasD. SimolaN. MartinoliM.G. Dopaminergic neurodegeneration in a rat model of long-term hyperglycemia: Preferential degeneration of the nigrostriatal motor pathway.Neurobiol. Aging20186911712810.1016/j.neurobiolaging.2018.05.01029890391
     [Google Scholar]
  9. SharmaT. KaurD. GrewalA.K. SinghT.G. Therapies modulating insulin resistance in Parkinson’s disease: A cross talk.Neurosci. Lett.202174913575410.1016/j.neulet.2021.13575433610666
     [Google Scholar]
  10. DaiC. TanC. ZhaoL. LiangY. LiuG. LiuH. ZhongY. LiuZ. MoL. LiuX. ChenL. Glucose metabolism impairment in Parkinson’s disease.Brain Res. Bull.202319911067210.1016/j.brainresbull.2023.11067237210012
     [Google Scholar]
  11. RehmanH.U. Kaleemullah AbdulM.T. Demonstration of precise relationships and links between type 2 diabetes mellitus, insulin resistance and Parkinson’s disease.Int. J. Res. - Granthaalayah202071225927010.29121/granthaalayah.v7.i12.2019.320
     [Google Scholar]
  12. LabandeiraC.M. Fraga-BauA. Arias RonD. MuñozA. Alonso-LosadaG. KoukoulisA. Romero-LopezJ. Rodriguez-PerezA.I. Diabetes, insulin and new therapeutic strategies for Parkinson’s disease: Focus on glucagon-like peptide-1 receptor agonists.Front. Neuroendocrinol.20216210091410.1016/j.yfrne.2021.10091433845041
     [Google Scholar]
  13. Ruiz-PozoV.A. Tamayo-TrujilloR. Cadena-UllauriS. Frias-ToralE. Guevara-RamírezP. Paz-CruzE. ChapelaS. MontalvánM. Morales-LópezT. Simancas-RacinesD. ZambranoA.K. The molecular mechanisms of the relationship between insulin resistance and Parkinson’s disease pathogenesis.Nutrients20231516358510.3390/nu1516358537630775
     [Google Scholar]
  14. DasR.R. UngerM.M. Diabetes and Parkinson disease.Neurology2018901986987010.1212/WNL.000000000000547029626175
     [Google Scholar]
  15. GaoY. BielohubyM. FlemingT. GrabnerG.F. FoppenE. BernhardW. Guzmán-RuizM. LayritzC. LegutkoB. ZinserE. García-CáceresC. BuijsR.M. WoodsS.C. KalsbeekA. SeeleyR.J. NawrothP.P. BidlingmaierM. TschöpM.H. YiC.X. Dietary sugars, not lipids, drive hypothalamic inflammation.Mol. Metab.20176889790810.1016/j.molmet.2017.06.00828752053
     [Google Scholar]
  16. Pérez-TaboadaI. AlberquillaS. MartínE.D. AnandR. Vietti-MichelinaS. TebekaN.N. CantleyJ. CraggS.J. MoratallaR. VallejoM. Diabetes causes dysfunctional dopamine neurotransmission favoring nigrostriatal degeneration in mice.Mov. Disord.20203591636164810.1002/mds.2812432666590
     [Google Scholar]
  17. Juárez-FloresD.L. EzquerraM. Gonzàlez-CasacubertaI. OrmazabalA. MorénC. TolosaE. FuchoR. Guitart-MampelM. CasadoM. ValldeoriolaF. de la Torre-LaraJ. MuñozE. TobíasE. ComptaY. García-GarcíaF.J. García-RuizC. Fernandez-ChecaJ.C. MartíM.J. GrauJ.M. CardellachF. ArtuchR. Fernández-SantiagoR. GarrabouG. Disrupted mitochondrial and metabolic plasticity underlie comorbidity between age-related and degenerative disorders as Parkinson disease and type 2 diabetes mellitus.Antioxidants2020911106310.3390/antiox911106333143119
     [Google Scholar]
  18. FakhruddinS. AlanaziW. JacksonK.E. Diabetes-induced reactive oxygen species: Mechanism of their generation and role in renal injury.J. Diabetes Res.2017201713010.1155/2017/837932728164134
     [Google Scholar]
  19. BenchoulaK. AryaA. ParharI.S. HwaW.E. FoxO1 signaling as a therapeutic target for type 2 diabetes and obesity.Eur. J. Pharmacol.202017375810.1016/j.ejphar33249079
     [Google Scholar]
  20. HariharanM. Effects of insulin on synapse formation and function; A possible role for insulin resistance.Thesis, Dalhousie University Halifax, Nova Scotia2012
     [Google Scholar]
  21. WanQ. XiongZ.G. ManH.Y. AckerleyC.A. BrauntonJ. LuW.Y. BeckerL.E. MacDonaldJ.F. WangY.T. Recruitment of functional GABAA receptors to postsynaptic domains by insulin.Nature1997388664368669010.1038/417929262404
     [Google Scholar]
  22. LeeJ.W. ChunW. LeeH.J. KimS.M. MinJ.H. KimD.Y. KimM.O. RyuH.W. LeeS.U. The role of microglia in the development of neurodegenerative diseases.Biomedicines2021910144910.3390/biomedicines910144934680566
     [Google Scholar]
  23. HongC.T. ChenK.Y. WangW. ChiuJ.Y. WuD. ChaoT.Y. HuC.J. ChauK.Y. BamoduO. Insulin resistance promotes Parkinson’s disease through aberrant expression of α-synuclein, mitochondrial dysfunction, and deregulation of the polo-like kinase 2 signaling.Cells20209374010.3390/cells903074032192190
     [Google Scholar]
  24. WatanabeT. SaotomeM. NobuharaM. SakamotoA. UrushidaT. KatohH. SatohH. FunakiM. HayashiH. Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance.Exp. Cell Res.2014323231432510.1016/j.yexcr.2014.02.027
     [Google Scholar]
  25. RuegseggerG.N. CreoA.L. CortesT.M. DasariS. NairK.S. Altered mitochondrial function in insulin-deficient and insulin-resistant states.J. Clin. Invest.201812893671368110.1172/JCI120843
     [Google Scholar]
  26. VogelT. Insulin/IGF-signalling in embryonic and adult neural proliferation and differentiation in the mammalian central nervous system.Trends in Cell Signaling Pathways in Neuronal Fate DecisionIntechOpenCroatia, Rijeka Wislet-GendebienS. 201310.5772/54946
     [Google Scholar]
  27. CheongJ.L.Y. de Pablo-FernandezE. FoltynieT. NoyceA.J. The association between type 2 diabetes mellitus and Parkinson’s disease.J. Parkinsons Dis.202010377578910.3233/JPD‑19190032333549
     [Google Scholar]
  28. ImamuraK. HishikawaN. SawadaM. NagatsuT. YoshidaM. HashizumeY. Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains.Acta Neuropathol.2003106651852610.1007/s00401‑003‑0766‑214513261
     [Google Scholar]
  29. KimD.S. ChoiH.I. WangY. LuoY. HofferB.J. GreigN.H. A new treatment strategy for Parkinson’s disease through the gut-brain axis: The glucagon-like peptide-1 receptor pathway.Cell Transplant.20172691560157110.1177/096368971772123429113464
     [Google Scholar]
  30. BartelsA.L. WillemsenA.T.M. DoorduinJ. de VriesE.F.J. DierckxR.A. LeendersK.L. [11C]-PK11195 PET: Quantification of neuroinflammation and a monitor of anti-inflammatory treatment in Parkinson’s disease?Parkinsonism Relat. Disord.2010161575910.1016/j.parkreldis.2009.05.00519487152
     [Google Scholar]
  31. ChenH. O’ReillyE.J. SchwarzschildM.A. AscherioA. Peripheral inflammatory biomarkers and risk of Parkinson’s disease.Am. J. Epidemiol.20071671909510.1093/aje/kwm26017890755
     [Google Scholar]
  32. Vicente MirandaH. El-AgnafO.M.A. OuteiroT.F. Glycation in Parkinson’s disease and Alzheimer’s disease.Mov. Disord.201631678279010.1002/mds.2656626946341
     [Google Scholar]
  33. CacabelosR. Parkinson’s disease: From pathogenesis to pharmacogenomics.Int. J. Mol. Sci.201718355110.3390/ijms1803055128273839
     [Google Scholar]
  34. PrajapatiA.K. GairolaA. MansuriM. Insulin resistance and neurodegenerative diseases.IP Int. J. Compr. Adv. Pharmacol.202492879010.18231/j.ijcaap.2024.013
     [Google Scholar]
  35. ZagareA. KurlovicsJ. AlmeidaC. FerranteD. Insulin resistance compromises midbrain organoid neural activity and metabolic efficiency predisposing to Parkinson’s disease pathology.bioRxiv202410.1101/2024.05.03.592331
     [Google Scholar]
  36. AndradeL.J.d.O. de OliveiraL.M. BittencourtA.M.V. LourençoL.G.d.C. de OliveiraG.C.M. Analysis of link between brain insulin resistance and Alzheimer’s disease: A systematic review.Res. Sq.202310.21203/rs.3.rs‑2852332/v1
     [Google Scholar]
  37. ShenJ. WangX. WangM. ZhangH. Potential molecular mechanism of exercise reversing insulin resistance and improving neurodegenerative diseases.Front. Physiol.202415133744210.3389/fphys.2024.133744238818523
     [Google Scholar]
  38. Md RazipN.N. Mohd NoorS. NorazitA. NordinN. SakehN.M. Khaza’aiH. An association between insulin resistance and neurodegeneration in zebrafish larval model (Danio rerio).Int. J. Mol. Sci.20222315829010.3390/ijms23158290
     [Google Scholar]
  39. BrauerR. WeiL. MaT. AthaudaD. GirgesC. VijiaratnamN. AuldG. WhittleseaC. WongI. FoltynieT. Diabetes medications and risk of Parkinson’s disease: A cohort study of patients with diabetes.Brain2020143103067307610.1093/brain/awaa26233011770
     [Google Scholar]
  40. BoccardiV. MuraseccoI. MecocciP. Diabetes drugs in the fight against Alzheimer’s disease.Ageing Res. Rev.20195410093610.1016/j.arr.2019.10093631330313
     [Google Scholar]
  41. CardosoS. MoreiraP.I. Antidiabetic drugs for Alzheimer’s and Parkinson’s diseases: Repurposing insulin, metformin, and thiazolidinediones.Int. Rev. Neurobiol.2020155376410.1016/bs.irn.2020.02.01032854858
     [Google Scholar]
  42. HölscherC. First clinical data of the neuroprotective effects of nasal insulin application in patients with Alzheimer’s disease.Alzheimers Dement.201410Suppl 1S33S3710.1016/j.jalz.2013.12.00624529523
     [Google Scholar]
  43. FineJ.M. StroebelB.M. FaltesekK.A. TeraiK. HaaseL. KnutzenK.E. KosyakovskyJ. BoweT.J. FullerA.K. FreyW.H. HansonL.R. Intranasal delivery of low-dose insulin ameliorates motor dysfunction and dopaminergic cell death in a 6-OHDA rat model of Parkinson’s disease.Neurosci. Lett.202071413456710.1016/j.neulet.2019.13456731629033
     [Google Scholar]
  44. PangY. LinS. WrightC. ShenJ. CarterK. BhattA. FanL.W. Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviates motor deficits induced by 6-OHDA in rats.Neuroscience201631815716510.1016/j.neuroscience.2016.01.02026777890
     [Google Scholar]
  45. PangY. FanL-W. CarterK. BhattA. Rapid transport of insulin to the brain following intranasal administration in rats.Neural Regen. Res.20191461046105110.4103/1673‑5374.25062430762017
     [Google Scholar]
  46. CraftS. BakerL.D. MontineT.J. MinoshimaS. WatsonG.S. ClaxtonA. ArbuckleM. CallaghanM. TsaiE. PlymateS.R. GreenP.S. LeverenzJ. CrossD. GertonB. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: A pilot clinical trial.Arch. Neurol.2012691293810.1001/archneurol.2011.23321911655
     [Google Scholar]
  47. KimJ. LeeS. Metformin activates AMPK and improves motor function in a mouse model of Parkinson’s disease.J. Neurosci. Res.2018966931941
     [Google Scholar]
  48. LuM. SuC. QiaoC. BianY. DingJ. HuG. Metformin prevents dopaminergic neuron death in MPTP/P-induced mouse model of Parkinson’s disease via autophagy and mitochondrial ROS clearance.Int. J. Neuropsychopharmacol.2016199pyw04710.1093/ijnp/pyw04727207919
     [Google Scholar]
  49. PatilS.P. JainP.D. GhumatkarP.J. TambeR. SathayeS. Neuroprotective effect of metformin in MPTP-induced Parkinson’s disease in mice.Neuroscience201427774775410.1016/j.neuroscience.2014.07.04625108167
     [Google Scholar]
  50. Pérez-RevueltaB.I. HettichM.M. CiociaroA. RotermundC. KahleP.J. KraussS. Di MonteD.A. Metformin lowers Ser-129 phosphorylated α-synuclein levels via mTOR-dependent protein phosphatase 2A activation.Cell Death Dis.201455e120910.1038/cddis.2014.17524810045
     [Google Scholar]
  51. SaewaneeN PraputpittayaT MalaiwongN ChalorakP MeemonK Neuroprotective effect of metformin on dopaminergic neurodegeneration and α-synuclein aggregation in C. elegans model of Parkinson’s disease.J. Neurosci. Res.1621321201910.1016/j.neures.2019.12.017
     [Google Scholar]
  52. SalcedoI. TweedieD. LiY. GreigN.H. Neuroprotective and neurotrophic actions of glucagon‐like peptide‐1: An emerging opportunity to treat neurodegenerative and cerebrovascular disorders.Br. J. Pharmacol.201216651586159910.1111/j.1476‑5381.2012.01971.x22519295
     [Google Scholar]
  53. BomfimT.R. Forny-GermanoL. SathlerL.B. Brito-MoreiraJ. HouzelJ.C. DeckerH. SilvermanM.A. KaziH. MeloH.M. McCleanP.L. HolscherC. ArnoldS.E. TalbotK. KleinW.L. MunozD.P. FerreiraS.T. De FeliceF.G. An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease–associated Aβ oligomers.J. Clin. Invest.201212241339135310.1172/JCI5725622476196
     [Google Scholar]
  54. GirgesC. VijiaratnamN. AthaudaD. AuldG. GandhiS. FoltynieT. The future of incretin-based approaches for neurodegenerative diseases in older adults: Which to choose? A review of their potential efficacy and suitability.Drugs Aging202138535537310.1007/s40266‑021‑00853‑733738783
     [Google Scholar]
  55. ZhangL. LiC. ZhangZ. ZhangZ. JinQ-Q. LiL. HölscherC. DA5-CH and Semaglutide protect against Neurodegeneration and Reduce α-Synuclein levels in the 6-OHDA Parkinson’s disease rat model.Parkinsons Dis.2022202211110.1155/2022/1428817
     [Google Scholar]
  56. CaoB. ZhangY. ChenJ. WuP. DongY. WangY. Neuroprotective effects of liraglutide against inflammation through the AMPK/NF-κB pathway in a mouse model of Parkinson’s disease.Metab. Brain Dis.202237245146210.1007/s11011‑021‑00879‑134817756
     [Google Scholar]
  57. ElbassuoniE.A. AhmedR.F. Mechanism of the neuroprotective effect of GLP-1 in a rat model of Parkinson’s with pre-existing diabetes.Neurochem. Int.201913110458310.1016/j.neuint.2019.10458331654678
     [Google Scholar]
  58. PariyarR. BastolaT. LeeD.H. SeoJ. Neuroprotective effects of the DPP4 inhibitor vildagliptin in in vivo and in vitro models of Parkinson’s disease.Int. J. Mol. Sci.2022234238810.3390/ijms2304238835216503
     [Google Scholar]
  59. MichelH.E. TadrosM.M. HendyM.S. MowakaS. AyoubB.M. Omarigliptin attenuates rotenone-induced Parkinson’s disease in rats: Possible role of oxidative stress, endoplasmic reticulum stress and immune modulation.Food Chem. Toxicol.202216411301510.1016/j.fct.2022.113015
     [Google Scholar]
  60. AbhangiK.V. PatelJ.I. Neuroprotective effects of linagliptin in a rotenone-induced rat model of Parkinson’s disease.Indian J. Pharmacol.2022541465010.4103/ijp.IJP_384_2035343207
     [Google Scholar]
  61. YuH.Y. SunT. WangZ. LiH. XuD. AnJ. WenL.L. LiJ.Y. LiW. FengJ. Exendin-4 and linagliptin attenuate neuroinflammation in a mouse model of Parkinson’s disease.Neural Regen. Res.20231881818182610.4103/1673‑5374.36024236751811
     [Google Scholar]
  62. ElGamalR.Z. TadrosM.G. EstherT.M. Linagliptin counteracts rotenone’s toxicity in non-diabetic rat model of Parkinson’s disease: Insights into the neuroprotective roles of DJ-1, SIRT-1/Nrf-2 and implications of HIF1-α.Eur. J. Pharmacol.202394117549810.1016/j.ejphar.2023.175498
     [Google Scholar]
  63. MarwaS. AbdelkaderN.F. RamadanE. Novel mechanistic insights towards the repositioning of alogliptin in Parkinson’s disease.Life Sci.202128710.1016/j.lfs.2021.120132
     [Google Scholar]
  64. Gopar-CuevasY. Saucedo-CardenasO. Loera-AriasM.J. Montes-de-Oca-LunaR. Rodriguez-RochaH. Garcia-GarciaA. Metformin and trehalose-modulated autophagy exerts a neurotherapeutic effect on Parkinsonʼs disease.Mol. Neurobiol.202360127253727310.1007/s12035‑023‑03530‑537542649
     [Google Scholar]
  65. MorD.E. SohrabiS. KaletskyR. KeyesW. TarticiA. KaliaV. Metformin rescues Parkinson’s disease phenotypes caused by hyperactive mitochondria.Proc. Natl. Acad. Sci.202011742264382644710.1073/pnas.2009838117
     [Google Scholar]
  66. HuotP. JohnstonT.H. FoxS.H. BrotchieJ.M. Pioglitazone may impair L‐DOPA anti‐parkinsonian efficacy in the MPTP‐lesioned macaque: Results of a pilot study.Synapse20156939910210.1002/syn.2180125559284
     [Google Scholar]
  67. MousaS. AyoubB. Repositioning of dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 agonists as potential neuroprotective agents.Neural Regen. Res.201914574574810.4103/1673‑5374.24921730688255
     [Google Scholar]
  68. SvenningssonP. WirdefeldtK. YinL. FangF. MarkakiI. EfendicS. LudvigssonJ.F. Reduced incidence of Parkinson’s disease after dipeptidyl peptidase-4 inhibitors-A nationwide case-control study.Mov. Disord.20163191422142310.1002/mds.2673427431803
     [Google Scholar]
  69. AthaudaD. EvansJ. WernickA. VirdiG. ChoiM.L. LawtonM. VijiaratnamN. GirgesC. Ben-ShlomoY. IsmailK. MorrisH. GrossetD. FoltynieT. GandhiS. The impact of type 2 diabetes in Parkinson’s disease.Mov. Disord.20223781612162310.1002/mds.2912235699244
     [Google Scholar]
  70. JankovicJ. PoeweW. Therapeutic strategies in Parkinson’s disease.J. Neurol.20122591120512061
     [Google Scholar]
  71. ChohanH. SenkevichK. PatelR.K. BestwickJ.P. JacobsB.M. Bandres CigaS. Gan-OrZ. NoyceA.J. Type 2 diabetes as a determinant of Parkinson’s disease risk and progression.Mov. Disord.20213661420142910.1002/mds.2855133682937
     [Google Scholar]
  72. OgakiK. FujitaH. NozawaN. ShiinaT. SakuramotoH. SuzukiK. Impact of diabetes and glycated hemoglobin level on the clinical manifestations of Parkinson’s disease.J. Neurol. Sci.202345412085110.1016/j.jns.2023.12085137931442
     [Google Scholar]
  73. BiesselsG.J. ReaganL.P. Hippocampal insulin resistance and cognitive dysfunction.Nat. Rev. Neurosci.2015161166067110.1038/nrn401926462756
     [Google Scholar]
  74. BiesselsG.J. StrachanM.W.J. VisserenF.L.J. KappelleL.J. WhitmerR.A. Dementia and cognitive decline in type 2 diabetes and prediabetic stages: Towards targeted interventions.Lancet Diabetes Endocrinol.20142324625510.1016/S2213‑8587(13)70088‑324622755
     [Google Scholar]
  75. KoekkoekP.S. KappelleL.J. van den BergE. RuttenG.E.H.M. BiesselsG.J. Cognitive function in patients with diabetes mellitus: Guidance for daily care.Lancet Neurol.201514332934010.1016/S1474‑4422(14)70249‑225728442
     [Google Scholar]
  76. LuchsingerJ.A. Adiposity, hyperinsulinemia, diabetes and Alzheimer’s disease.Eur. J. Pharmacol.2008585111912910.1016/j.ejphar.2008.02.04818384771
     [Google Scholar]
  77. NortonS. MatthewsF.E. BarnesD.E. YaffeK. BrayneC. Potential for primary prevention of Alzheimer’s disease: An analysis of population-based data.Lancet Neurol.201413878879410.1016/S1474‑4422(14)70136‑X25030513
     [Google Scholar]
  78. KiliaanA.J. ArnoldussenI.A.C. GustafsonD.R. Adipokines: A link between obesity and dementia?Lancet Neurol.201413991392310.1016/S1474‑4422(14)70085‑725142458
     [Google Scholar]
  79. RatajskaA. EtheridgeC.B. LopezF.V. KenneyL. RodriguezK. SchadeR.N. The relationship between autonomic dysfunction and mood symptoms in de novo Parkinson’s disease patients over time.J. Geriatr. Psychiatry Neurol.202337324225210.1177/0891988723120454237831611
     [Google Scholar]
  80. LiuS. LiuC. HuW. JiY. Frequency, severity, and duration of autonomic symptoms in patients of prodromal dementia with lewy bodies.J. Alzheimers Dis.202289392392910.3233/JAD‑22027535988221
     [Google Scholar]
  81. MerolaA. RomagnoloA. RossoM. SuriR. BerndtZ. MauleS. LopianoL. EspayA.J. Autonomic dysfunction in Parkinson’s disease: A prospective cohort study.Mov. Disord.201833339139710.1002/mds.2726829278286
     [Google Scholar]
  82. KalinderiK. PapaliagkasV. FidaniL. Current genetic data on depression and anxiety in Parkinson’s disease patients.Parkinsonism Relat. Disord.202311810592210.1016/j.parkreldis.2023.10592237935601
     [Google Scholar]
  83. CaldarovA.R. GavriliucO. RotaruL. AndruscaA. FalaP. GavriliucM. Comorbidities in patients with Parkinson's disease Associated diseases in patients with Parkinson's disease.Bull. Acad. Sci. Mold. Med. Sci.2022371303410.52692/1857‑0011.2021.3‑71.25
     [Google Scholar]
  84. KellyO. SullivanJ. CarrisN. GeciS. MartinezA. LiashenkoV. ColvinJ. MiskoE. VanderlaanG. LiuH. DalviP.S. The impact of diabetes mellitus on the development of psychiatric and neurological disorders.Brain Disord.20241410013510.1016/j.dscb.2024.100135
     [Google Scholar]
  85. LiS. YangD. ZhouX. ChenL. LiuL. LinR. Neurological and metabolic related pathophysiologies and treatment of comorbid diabetes with depression.CNS Neurosci. Ther.2023304e1449710.1111/cns.1449737927197
     [Google Scholar]
  86. ShehataG.A. FarweezH.M. AliA.M. HassanH.S. TohamyA.M. MostafaM. IbrahimM.A. TarekK. ElrashedyA.A. AbdelnabyR. ElsayedM. GaberD.E. Impact of Parkinsonism comorbid depression on cognitive functions.Egypt. J. Neurol. Psychiat. Neurosurg.20246013710.1186/s41983‑024‑00813‑z
     [Google Scholar]
  87. HookmanP. Gastrointestinal manifestations of Parkinson’s disease survey of the recent literature.Jpn. J. Res.2024521410.33425/2690‑8077.1102
     [Google Scholar]
  88. TanA.H. ChuahK.H. BehY.Y. ScheeJ.P. MahadevaS. LimS.Y. Gastrointestinal dysfunction in Parkinson’s disease: Neuro-gastroenterology perspectives on a multifaceted problem.J. Mov. Disord.202316213815110.14802/jmd.2222037258277
     [Google Scholar]
  89. WarneckeT. SchäferK-H. ClausI. Del TrediciK. JostW.H. Gastrointestinal involvement in Parkinson’s disease: Pathophysiology, diagnosis, and management.NPJ Parkinsons Dis.2022813110.1038/s41531‑022‑00295‑x
     [Google Scholar]
  90. ScorzaF.A. de AlmeidaA-C.G. ScorzaC.A. FinstererJ. Gastrointestinal dysfunctions and sudden death in Parkinson patients: Domperidone in FOCUS.J. Investig. Med.202371554054110.1177/10815589231161003
     [Google Scholar]
  91. ChohanH. KonstantinS. KonstantinS.R. Type 2 diabetes as a determinant of Parkinson’s disease risk and progression.medRxiv202010.1101/2020.11.12.20230474
     [Google Scholar]
  92. de Pablo-FernándezE. CourtneyR. RockliffeA. GentlemanS. HoltonJ.L. WarnerT.T. Faster disease progression in Parkinson’s disease with type 2 diabetes is not associated with increased α‐synuclein, tau, amyloid‐β or vascular pathology.Neuropathol. Appl. Neurobiol.20214771080109110.1111/nan.1272833969516
     [Google Scholar]
  93. Ko-EunC. Dong-WooR. OhY.-S. KimJ.-S. Fasting plasma glucose levels and longitudinal motor and cognitive outcomes in Parkinson’s disease patients.J. Mov. Disord.202417219820710.14802/jmd.23264
     [Google Scholar]
  94. VladuM. ClenciuD. BîcuM. MofaM. The prognosis of patients with chronic kidney disease and diabetes mellitus.Rom. J. Diabetes Nutr. Metab. Dis.201421320321210.2478/rjdnmd‑2014‑0025
     [Google Scholar]
  95. LvY.Q. YuanL. SunY. DouH.W. SuJ.H. HouZ.P. LiJ.Y. LiW. Long-term hyperglycemia aggravates α-synuclein aggregation and dopaminergic neuronal loss in a Parkinson’s disease mouse model.Transl. Neurodegener.20221111410.1186/s40035‑022‑00288‑z35255986
     [Google Scholar]
  96. LabandeiraC.M. Fraga-BauA. Arias RonD. Alvarez-RodriguezE. Vicente-AlbaP. Lago-GarmaJ. Rodriguez-PerezA.I. Parkinson’s disease and diabetes mellitus: Common mechanisms and treatment repurposing.Neural Regen. Res.2022178165210.4103/1673‑5374.332122
     [Google Scholar]
  97. ChungK-M. HoC-H. ChenY-C. HsuC-C. LinH-J. WangJ-J. TsaiK-T. HuangC-C. Hyperglycemic crisis and Parkinson disease: A retrospective cohort study based on nationwide data.Arch. Med. Sci.202310.5114/aoms/159603
     [Google Scholar]
  98. BorislavI. AraK. MargaritaG. IliyaD. NadezhdaD. Diabetes mellitus in Parkinson`s disease patients.Scr. Sci. Med.2013451798110.14748/ssm.v45i1.346
     [Google Scholar]
/content/journals/cst/10.2174/0115743624334102241115162404
Loading
Type 2 Diabetes Mellitus and Parkinson's Disease: An Emerging Link
Current Signal Transduction Therapy 20, E15743624334102 (2025); https://doi.org/10.2174/0115743624334102241115162404
/content/journals/cst/10.2174/0115743624334102241115162404
/content/journals/cst/10.2174/0115743624334102241115162404
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): antidiabetic drugs; insulin; Parkinson’s disease; PI3K; prognosis; type 2 diabetes mellitus
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test