The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Troshneva A.Yu.

Russian Medical Academy for Continuous Professional Education

Ametov A.S.

Russian Medical Academy of Continuing Postgraduate Education

Parkinson’s disease and type 2 diabetes mellitus: interrelation of pathogenetic mechanisms and general therapeutic approaches

Authors:

Troshneva A.Yu., Ametov A.S.

More about the authors

Read: 4023 times


To cite this article:

Troshneva AYu, Ametov AS. Parkinson’s disease and type 2 diabetes mellitus: interrelation of pathogenetic mechanisms and general therapeutic approaches. S.S. Korsakov Journal of Neurology and Psychiatry. 2022;122(11‑2):12‑18. (In Russ.)
https://doi.org/10.17116/jnevro202212211212

Recommended articles:
Sarcopenia as a non-motor symptom of Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(9):15-22
Asso­ciation of inflammation and chro­nic fati­gue syndrome in patients with Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(9):79-87
Surgical treatment of macromastia in benign breast dysplasia and como­rbidities. Plastic Surgery and Aesthetic Medi­cine. 2024;(4-2):5-13
Diagnosis and treatment approaches for sialorrhea in patients with Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(10):29-34
Neurochemical mechanisms of tremor in Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(11):64-72

References:

  1. Mhyre TR, Boyd JT, Hamill RW, Maguire-Zeiss KA. Parkinson’s disease. SubcellBiochem. 2012;65:389-455.  https://doi.org/10.1007/978-94-007-5416-4_16
  2. GBD 2016 Parkinson’s Disease Collaborators. Global, regional, and national burden of Parkinson’s disease, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016 [published correction appears in Lancet Neurol. 2021 Dec;20(12):e7]. Lancet Neurol. 2018;17(11):939-953.  https://doi.org/10.1016/S1474-4422(18)30295-3
  3. Illarioshkin SN. Modern view on etiology of Parkinson’s disease. The Neurological Journal. 2015;20(4):4-13. (In Russ.). https://doi.org/10.18821/1560-9545-2015-20-4-4-13
  4. Veryugina NI, Levin OS, Lyashenko EA. Neuroendocrine and metabolic impairments in patients with Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. Special issues. 2020;120(10-2):67-73. (In Russ.). https://doi.org/10.17116/jnevro202012010267
  5. Hassan A, Sharma Kandel R, et al. Diabetes Mellitus and Parkinson’s Disease: Shared Pathophysiological Links and Possible Therapeutic Implications. Cureus. 2020;12(8):e9853. https://doi.org/10.7759/cureus.9853
  6. Athauda D, Foltynie T. Insulin resistance and Parkinson’s disease: A new target for disease modification? Prog Neurobiol. 2016;145-146:98-120.  https://doi.org/10.1016/j.pneurobio.2016.10.001
  7. Aviles-Olmos I, Limousin P, Lees A, Foltynie T. Parkinson’s disease, insulin resistance and novel agents of neuroprotection. Brain. 2013;136(Pt 2): 374-384.  https://doi.org/10.1093/brain/aws009
  8. Santiago JA, Potashkin JA. Shared dysregulated pathways lead to Parkinson’s disease and diabetes. Trends Mol Med. 2013;9:176-186.  https://doi.org/10.1016/j.molmed.2013.01.002
  9. Craft S, Watson GS. Insulin and neurodegenerative disease: Shared and specific mechanisms, Lancet Neurol. 2004;3:169-178.  https://doi.org/10.1016/s1474-4422(04)00681-7
  10. Biosa A, Outeiro TF, Bubacco L, Bisaglia M. Diabetes mellitus as a risk factor for Parkinson’s disease: A molecular point of view. Mol Neurobiol. 2018;55:8754-8763. https://doi.org/10.1007/s12035-018-1025-9
  11. Hölscher C. Brain insulin resistance: role in neurodegenerative disease and potential for targeting. Expert OpinInvestig Drugs. 2020 Apr;29(4):333-348. Epub 2020 Mar 16.  https://doi.org/10.1080/13543784.2020.1738383
  12. Kabir M, Ferdous Mitu J, Akter R, et al. Therapeutic potential of dopamine agonists in the treatment of type 2 diabetes mellitus. Environmental Science and Pollution Research. 2022;29(31):46385-46404. https://doi.org/10.1007/s11356-022-20445-1
  13. Pagano G, Polychronis S, Wilson H, et al. Diabetes mellitus and Parkinson disease. Neurology. 2018;90(19):e1654-e1662. https://doi.org/10.1212/wnl.0000000000005475
  14. Ben-Joseph A, Haque T, Gallagher D, et al. Type 2 diabetes mellitus may worsen severity of motor symptoms in people with Parkinson’s disease [abstract]. Mov Disord. 2020;35(Suppl 1):S153. https://doi.org/10.1002/mds.28268
  15. Hussein M, Khamis A, Soliman R, Ali S. Metabolic syndrome and insulin resistance in Parkinson’s disease: could they affect motor or cognitive symptoms? [abstract]. Mov Disord. 2019;34(Suppl 2). Accessed September 18, 2021. https://doi.org/10.1002/mds.v34.s2
  16. Palacios N, Gao X, McCullough ML, et al. Obesity, diabetes, and risk of parkinson’s disease. Movement Disorders. 2011;26(12):2253-2259. https://doi.org/10.1002/mds.23855
  17. Lu L, Fu D, Li H, et al. Diabetes and Risk of Parkinson’s Disease: An Updated Meta-Analysis of Case-Control Studies. PLoS One. 2014;9(1):e85781. https://doi.org/10.1371/journal.pone.0085781
  18. Cheong J, de Pablo-Fernandez E, Foltynie T, Noyce A. The Association Between Type 2 Diabetes Mellitus and Parkinson’s Disease. J Parkinsons Dis. 2020;10(3):775-789.  https://doi.org/10.3233/jpd-191900
  19. De Iuliis A, Montinaro E, Fatati G, et al. Diabetes mellitus and Parkinson’s disease: dangerous liaisons between insulin and dopamine. Neural Regen Res. 2022;17(3):523-533.  https://doi.org/10.4103/1673-5374.320965
  20. Martinez-Valbuena I, Valenti-Azcarate R, Amat-Villegas I, et al. Mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion protein. Acta Neuropathol Commun. 2021;9(1):Article 64.  https://doi.org/10.1186/s40478-021-01171-0
  21. Delamarre A, Rigalleau V, Meissner W. Insulin resistance, diabetes and Parkinson’s disease: The match continues. Parkinsonism Relat Disord. 2020;80: 199-200.  https://doi.org/10.1016/j.parkreldis.2020.10.013
  22. Mollenhauer B, Zimmermann J, Sixel‐Döring F, et al. Baseline predictors for progression 4 years after Parkinson’s disease diagnosis in the De Novo Parkinson Cohort (DeNoPa). Movement Disorders. 2018;34(1):67-77.  https://doi.org/10.1002/mds.27492
  23. Mucibabic M, Steneberg P, Lidh E, et al. α-Synuclein promotes IAPP fibril formation in vitro and β-cell amyloid formation in vivo in mice. Sci Rep. 2020;10(1):Article 20438. https://doi.org/10.1038/s41598-020-77409-z
  24. Elabi OF, Cunha JPMCM, Gaceb A, et al. High-fat diet-induced diabetes leads to vascular alterations, pericyte reduction, and perivascular depletion of microglia in a 6-OHDA toxin model of Parkinson disease. J Neuroinflammation. 2021;18(1):175.  https://doi.org/10.1186/s12974-021-02218-8
  25. Larsen MEC, Thykjaer AS, Pedersen FN, et al. Diabetic retinopathy as a potential marker of Parkinson’s disease: A register-based cohort study. Brain Commun. 2021;3(4):fcab262. https://doi.org/10.1093/braincomms/fcab262
  26. Mauricio D, Vlacho B, Barrot de la Puente J, et al. Associations Between Diabetic Retinopathy and Parkinson’s Disease: Results From the Catalonian Primary Care Cohort Study. Front Med (Lausanne). 2022;8:800973. Published 2022 Jan 18.  https://doi.org/10.3389/fmed.2021.800973
  27. Lv Y-Q, Yuan L, Sun Y, et al. Long-term hyperglycemia aggravates α-synuclein aggregation and dopaminergic neuronal loss in a Parkinson’s disease mouse model. Transl Neurodegener. 2022;11(1):14.  https://doi.org/10.1186/s40035-022-00288-z
  28. De Pablo‐Fernández E, Courtney R, Rockliffe A, et al. 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. 2021;47(7):1080-1091. https://doi.org/10.1111/nan.12728
  29. Milstein J, Ferris H. The brain as an insulin-sensitive metabolic organ. Mol Metab. 2021:101234. https://doi.org/10.1016/j.molmet.2021.101234
  30. Fiory F, Perruolo G, Cimmino I, et al. The Relevance of Insulin Action in the Dopaminergic System. Front Neurosci. 2019;13:Article 868.  https://doi.org/10.3389/fnins.2019.00868
  31. Spinelli M, Fusco S, Grassi C. Brain Insulin Resistance and Hippocampal Plasticity: Mechanisms and Biomarkers of Cognitive Decline. Front Neurosci. 2019;13:788.  https://doi.org/10.3389/fnins.2019.00788
  32. Duarte A, Moreira P, Oliveira C. Insulin in Central Nervous System: More than Just a Peripheral Hormone. J Aging Res. 2012;2012:1-21.  https://doi.org/10.1155/2012/384017
  33. Pomytkin I, Pinelis V. Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions. Life (Basel). 2021;11(3):262.  https://doi.org/10.3390/life11030262
  34. Ametov AS. Saharnyj diabet 2 tipa. Problemy i resheniya. M.: GEOTAR-Media; 2014:1032. ISBN 978-5-9704-2829-0. Accessed September 30, 2021. https://www.rosmedlib.ru/book/ISBN9785970428290.html
  35. Woert M, Mueller P. Glucose, insulin, and free fatty acid metabolism in Parkinson’s disease treated with levodopa. Clinical Pharmacology & Therapeutics. 1971;12(2 Part 2):360-367.  https://doi.org/10.1002/cpt1971122part2360
  36. Sandyk R. The Relationship Between Diabetes Mellitus and Parkinson’s Disease. International Journal of Neuroscience. 1993;69(1-4):125-130.  https://doi.org/10.3109/00207459309003322
  37. Marques A, Dutheil F, Durand E, et al. Glucose dysregulation in Parkinson’s disease: Too much glucose or not enough insulin? Parkinsonism Relat Disord. 2018;55:122-127.  https://doi.org/10.1016/j.parkreldis.2018.05.026
  38. Vikdahl M, Carlsson M, Linder J, et al. Weight gain and increased central obesity in the early phase of Parkinson’s disease. Clinical Nutrition. 2014; 33(6):1132-1139. https://doi.org/10.1016/j.clnu.2013.12.012
  39. Morales-Briceño H, Cervantes-Arriaga A, Rodríguez-Violante M, et al. Overweight is more prevalent in patients with Parkinson’s disease. Arq Neuropsiquiatr. 2012;70(11):843-846.  https://doi.org/10.1590/s0004-282x2012001100004
  40. Petroni M, Albani G, Bicchiega V, et al. Body composition in advanced-stage Parkinson’s disease. Acta Diabetol. 2003;40(0):s187-s190. https://doi.org/10.1007/s00592-003-0062-6
  41. Femat-Roldán G, Gaitán Palau M, Castilla-Cortázar I, et al. Altered Body Composition and Increased Resting Metabolic Rate Associated with the Postural Instability/Gait Difficulty Parkinson’s Disease Subtype. Parkinson’s Disease. 2020;2020:1-9.  https://doi.org/10.1155/2020/8060259
  42. Barichella M, Marczewska A, Mariani C, et al. Body weight gain rate in patients with Parkinson’s disease and deep brain stimulation. Movement Disorders. 2003;18(11):1337-1340. https://doi.org/10.1002/mds.10543
  43. Hogg E, Athreya K, Basile C, et al. High Prevalence of Undiagnosed Insulin Resistance in Non-Diabetic Subjects with Parkinson’s Disease. J Parkinsons Dis.2018;8(2):259-265.  https://doi.org/10.3233/jpd-181305
  44. Clegg DJ, Gotoh K, Kemp C, et al. Consumption of a high-fat diet induces central insulin resistance independent of adiposity. PhysiolBehav. 2011;103:10-16.  https://doi.org/10.1016/j.physbeh.2011.01.010
  45. Prasuhn J, Davis R, Kumar K. Targeting Mitochondrial Impairment in Parkinson’s Disease: Challenges and Opportunities. Front Cell Dev Biol. 2021;8.  https://doi.org/10.3389/fcell.2020.615461
  46. Salmina AB, Yauzina NA, Kuvacheva NV, et al. Insulin and insulin resistance: new molecule markers and target molecule for the diagnosis and therapy of diseases of the central nervous system. Bulletin of Siberian Medicine. 2013;12(5):104-118. (In Russ.). https://doi.org/10.20538/1682-0363-2013-5-104-118
  47. Rhea EM, Banks WA. Role of the Blood-Brain Barrier in Central Nervous System Insulin Resistance. Front Neurosci. 2019;13:521. Published 2019 June 04.  https://doi.org/10.3389/fnins.2019.00521
  48. Wu YC, Sonninen TM, Peltonen S, Koistinaho J, Lehtonen Š. Blood-Brain Barrier and Neurodegenerative Diseases-Modeling with iPSC-Derived Brain Cells. Int J Mol Sci. 2021;22(14):7710. Published 2021 July 19.  https://doi.org/10.3390/ijms22147710
  49. Hou X, Watzlawik J, Fiesel F, Springer W. Autophagy in Parkinson’s Disease. J Mol Biol. 2020;432(8):2651-2672. https://doi.org/10.1016/j.jmb.2020.01.037
  50. Liu XL, Wang YD, Yu XM, et al. Mitochondria-mediated damage to dopaminergic neurons in Parkinson’s disease (Review). Int J Mol Med. 2018;41(2):615-623.  https://doi.org/10.3892/ijmm.2017.3255
  51. Sripetchwandee J, Chattipakorn N, Chattipakorn SC. Links Between Obesity-Induced Brain Insulin Resistance, Brain Mitochondrial Dysfunction, and Dementia. Front Endocrinol (Lausanne).2018;9:496.  https://doi.org/10.3389/fendo.2018.00496
  52. Tagliati M, Hogg E, Wu T, et al. Central Insulin Resistance Index is Independent of Peripheral Insulin Resistance in Parkinson’s disease [abstract]. Mov Disord. 2019;34(Suppl 2). Accessed September 06, 2021. https://doi.org/10.1002/mds.v34.s2
  53. Kleinridders A, Cai W, Cappellucci L, et al. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. Proceedings of the National Academy of Sciences. 2015;112(11):3463-3468. https://doi.org/10.1073/pnas.1500877112
  54. Gao S, Duan C, Gao G, Wang X, Yang H. Alpha-synuclein overexpression negatively regulates insulin receptor substrate 1 by activating mTORC1/S6K1 signaling. Int J Biochem Cell Biol.2015;64:25-33.  https://doi.org/10.1016/j.biocel.2015.03.006
  55. Iravanpour F, Dargahi L, Rezaei M, et al. Intranasal insulin improves mitochondrial function and attenuates motor deficits in a rat 6‐OHDA model of Parkinson’s disease. CNS Neurosci Ther. 2021;27(3):308-319.  https://doi.org/10.1111/cns.13609
  56. Sharma SK, Chorell E, Steneberg P, et al. Insulin-degrading enzyme prevents α-synuclein fibril formation in a nonproteolytical manner. Sci Rep. 2015;5:12531. https://doi.org/10.1038/srep12531
  57. Cereda E, Barichella M, Cassani E, et al. Clinical features of Parkinson disease when onset of diabetes came first: A case-control study. Neurology. 2012;78(19):1507-1511. https://doi.org/10.1212/wnl.0b013e3182553cc9
  58. Chan H, Cheung Y, Chau D, et al. Metabolic syndrome: its link with motor function of Parkinson’s disease [abstract]. Mov Disord. 2017;32(Suppl 2): Abstract 522.  https://doi.org/10.1002/mds.27087
  59. Zittel S, Uyar M, Lezius S, et al. HbA1c and Motor Outcome in Parkinson’s Disease in the Mark‐PD Study. Movement Disorders. 2021;36(8):1991-1992. https://doi.org/10.1002/mds.28689
  60. Kotagal V, Albin R, Müller M, et al. Diabetes is associated with postural instability and gait difficulty in Parkinson disease. Parkinsonism Relat Disord. 2013;19(5):522-526.  https://doi.org/10.1016/j.parkreldis.2013.01.016
  61. Sharma T, Kaur D, Grewal AK, Singh TG. Therapies modulating insulin resistance in Parkinson’s disease: A cross talk. Neurosci Lett.2021;749:135754. https://doi.org/10.1016/j.neulet.2021.135754
  62. Meléndez-Flores J, Castillo-Torres S, Cerda-Contreras C, et al. Clinical features of metabolic syndrome in patients with Parkinson’s disease. Revista de Neurología. 2021;72(01):9-15.  https://doi.org/10.33588/rn.7201.2020323
  63. Chohan H, Senkevich K, Patel R, et al. Type 2 Diabetes as a Determinant of Parkinson’s Disease Risk and Progression. Movement Disorders. 2021;36(6):1420-1429. https://doi.org/10.1002/mds.28551
  64. Ashraghi MR, Pagano G, Polychronis S, et al. Parkinson’s disease, diabetes and cognitive impairment. Recent Pat Endocr Metab Immune Drug Discov. 2016;10:11-21.  https://doi.org/10.2174/1872214810999160628105549
  65. Bergantin LB. A Link Between Brain Insulin Resistance and Cognitive Dysfunctions: Targeting Ca2+/cAMP Signalling. Cent Nerv Syst Agents Med Chem. 2020;20(2):103-109.  https://doi.org/10.2174/1871524920666200129121232
  66. Willmann C, Brockmann K, Wagner R, et al. Insulin sensitivity predicts cognitive decline in individuals with prediabetes. BMJ Open Diabetes Res Care. 2020;8(2):e001741. https://doi.org/10.1136/bmjdrc-2020-001741
  67. Yoo H, Chung S, Lee P, et al. The Influence of Body Mass Index at Diagnosis on Cognitive Decline in Parkinson’s Disease. Journal of Clinical Neurology. 2019;15(4):517.  https://doi.org/10.3988/jcn.2019.15.4.517
  68. Kim H, Oh E, Lee J, et al. Relationship between changes of body mass index (BMI) and cognitive decline in Parkinson’s disease (PD). Arch Gerontol Geriatr. 2012;55(1):70-72.  https://doi.org/10.1016/j.archger.2011.06.022
  69. Lorefalt B, Ganowiak W, Palhagen S, et al. Factors of importance for weight loss in elderly patients with Parkinson’s disease. Acta Neurol Scand. 2004;110(3):180-187.  https://doi.org/10.1111/j.1600-0404.2004.00307.x
  70. Wills A, Li R, Pérez A, et al. Predictors of weight loss in early treated Parkinson’s disease from the NET-PDLS-1 cohort. J Neurol. 2017; 264(8):1746-1753. https://doi.org/10.1007/s00415-017-8562-4
  71. Yang L, Wang H, Liu L, Xie A. The Role of Insulin/IGF-1/PI3K/Akt/GSK3β Signaling in Parkinson’s Disease Dementia. Front Neurosci. 2018;12:Article 73.  https://doi.org/10.3389/fnins.2018.00073
  72. Bosco D, Plastino M, Cristiano D, et al. Dementia is associated with insulin resistance in patients with Parkinson’s disease. J Neurol Sci. 2012 Apr 15; 315(1-2):39-43.  https://doi.org/10.1016/j.jns.2011.12.008
  73. Gankina OA, Levin OS, Ilyasova FN. Cognitive Impairment in Patients with Metabolic Syndrome. Effective Pharmacotherapy. Endocrinology. 2016; 29(3):16-20. Accessed September 30, 2021. https://umedp.ru/upload/iblock/2a8/endo_03_2016.pdf
  74. Bergmans R, Rapp A, Kelly K, et al. Understanding the relationship between type 2 diabetes and depression: lessons from genetically informative study designs. Diabet Med. 2020;38(2):e14399. https://doi.org/10.1111/dme.14399
  75. Riederer P, Bartl J, Laux G, Grünblatt E. Diabetes Type II: A Risk Factor for Depression-Parkinson-Alzheimer? Neurotox Res. 2010;19(2):253-265.  https://doi.org/10.1007/s12640-010-9203-1
  76. Roh J, Lee S, Yoon J. Metabolic Syndrome and Parkinson’s Disease Incidence: A Nationwide Study Using Propensity Score Matching. Metab Syndr Relat Disord. 2021;19(1):1-7.  https://doi.org/10.1089/met.2020.0060
  77. Nam G, Kim S, Han K, et al. Metabolic syndrome and risk of Parkinson disease: A nationwide cohort study. PLoS Med. 2018;15(8):e1002640. https://doi.org/10.1371/journal.pmed.1002640
  78. Sääksjärvi K, Knekt P, Männistö S, et al. Prospective study on the components of metabolic syndrome and the incidence of Parkinson’s disease. Parkinsonism Relat Disord. 2015;21(10):1148-1155. https://doi.org/10.1016/j.parkreldis.2015.07.017
  79. Maraki MI, Yannakoulia M, Stamelou M, et al. Mediterranean diet adherence is related to reduced probability of prodromal Parkinson’s disease. Mov Disord. 2019;34(1):48-57.  https://doi.org/10.1002/mds.27489
  80. Cassani E, Barichella M, Ferri V, et al. Dietary habits in Parkinson’s disease: Adherence to Mediterranean diet. Parkinsonism RelatDisord.2017;42:40-46.  https://doi.org/10.1016/j.parkreldis.2017.06.007
  81. Fisher BE, Wu AD, Salem GJ, et al. The effect of exercise training in improving motor performance and corticomotor excitability in people with early Parkinson’s disease. Arch Phys Med Rehabil. 2008;89(7):1221-1229. https://doi.org/10.1016/j.apmr.2008.01.013
  82. Hölscher C. First clinical data of the neuroprotective effects of nasal insulin application in patients with Alzheimer’s disease. Alzheimers Dement. 2014;10(1 Suppl):S33-S37.  https://doi.org/10.1016/j.jalz.2013.12.006
  83. Hölscher C. Insulin Signaling Impairment in the Brain as a Risk Factor in Alzheimer’s Disease. Front Aging Neurosci. 2019;11:Article 88.  https://doi.org/10.3389/fnagi.2019.00088
  84. Yu YW, Hsueh SC, Lai JH, et al. Glucose-Dependent Insulinotropic Polypeptide Mitigates 6-OHDA-Induced Behavioral Impairments in Parkinsonian Rats. Int J Mol Sci. 2018;19(4):1153. https://doi.org/10.3390/ijms19041153
  85. Vaccari C, Grotto D, Pereira T, et al. GLP-1 and GIP receptor agonists in the treatment of Parkinson’s disease: Translational systematic review and meta-analysis protocol of clinical and preclinical studies. PLoS One. 2021;16(8):e0255726. https://doi.org/10.1371/journal.pone.0255726
  86. Zhou M, Chen S, Peng P, et al. Dulaglutide ameliorates STZ induced AD-like impairment of learning and memory ability by modulating hyperphosphorylation of tau and NFs through GSK3β. BiochemBiophys Res Commun. 2019;511(1):154-160.  https://doi.org/10.1016/j.bbrc.2019.01.103
  87. Wadden TA, Hollander P, Klein S, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study [published correction appears in Int J Obes (Lond). 2013 Nov;37(11):1514] [published correction appears in Int J Obes (Lond). 2015 Jan;39(1):187]. Int J Obes (Lond). 2013;37(11):1443-1451. https://doi.org/10.1038/ijo.2013.120
  88. Hamilton A, Hölscher C. Receptors for the incretin glucagon-like peptide-1 are expressed on neurons in the central nervous system. Neuroreport. 2009 Aug 26;20(13):1161-6.  https://doi.org/10.1097/WNR.0b013e32832fbf14
  89. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131-2157. https://doi.org/10.1053/j.gastro.2007.03.054
  90. Zhang L, Li L, Hölscher C. Semaglutide is Neuroprotective and Reduces α-Synuclein Levels in the Chronic MPTP Mouse Model of Parkinson’s Disease. J Parkinsons Dis. 2019;9(1):157-171.  https://doi.org/10.3233/jpd-181503
  91. Grieco M, Giorgi A, Gentile M, et al. Glucagon-Like Peptide-1: A Focus on Neurodegenerative Diseases. Front Neurosci. 2019;13:Article 1112. https://doi.org/10.3389/fnins.2019.01112
  92. Liu W, Jalewa J, Sharma M, et al. Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Neuroscience.2015;303:42-50.  https://doi.org/10.1016/j.neuroscience.2015.06.054
  93. Aviles-Olmos I, Dickson J, Kefalopoulou Z, et al. Exenatide and the treatment of patients with Parkinson’s disease. J Clin Invest. 2013;123(6):2730-2736. https://doi.org/10.1172/JCI68295
  94. Aviles-Olmos I, Dickson J, Kefalopoulou Z, et al. Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinson’s disease. J Parkinsons Dis. 2014;4(3):337-344.  https://doi.org/10.3233/JPD-140364
  95. Athauda D, Maclagan K, Skene S, et al. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. The Lancet. 2017;390(10103):1664-1675. https://doi.org/10.1016/s0140-6736(17)31585-4
  96. Zhu Y, Pu J, Chen Y, Zhang B. Decreased risk of Parkinson’s disease in diabetic patients with thiazolidinediones therapy: An exploratory meta-analysis. PLoS One. 2019;14(10):e0224236. https://doi.org/10.1371/journal.pone.0224236
  97. Brakedal B, Flønes I, Reiter SF, et al. Glitazone use associated with reduced risk of Parkinson’s disease. Mov Disord. 2017;32(11):1594-1599. https://doi.org/10.1002/mds.27128
  98. Wu HF, Kao LT, Shih JH, et al. Pioglitazone use and Parkinson’s disease: A retrospective cohort study in Taiwan. BMJ Open. 2018;8(8):e023302. https://doi.org/10.1136/bmjopen-2018-023302
  99. Saunders A, Burns D, Gottschalk W. Reassessment of Pioglitazone for Alzheimer’s Disease. Front Neurosci. 2021;15:Article 666958. https://doi.org/10.3389/fnins.2021.666958
  100. NINDS Exploratory Trials in Parkinson Disease (NET-PD) FS-ZONE Investigators. Pioglitazone in early Parkinson’s disease: A phase 2, multicentre, double-blind, randomised trial [published correction appears in Lancet Neurol. 2015 Oct; 14(10):979]. Lancet Neurol. 2015;14(8):795-803.  https://doi.org/10.1016/S1474-4422(15)00144-1
  101. Valencia W, Palacio A, Tamariz L, Florez H. Metformin and ageing: improving ageing outcomes beyond glycaemic control. Diabetologia. 2017;60(9):1630-1638. https://doi.org/10.1007/s00125-017-4349-5
  102. Łabuzek K, Suchy D, Gabryel B, et al. Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide. Pharmacological Reports. 2010;62(5):956-965.  https://doi.org/10.1016/s1734-1140(10)70357-1
  103. Shi Q, Liu S, Fonseca V, et al. Effect of metformin on neurodegenerative disease among elderly adult US veterans with type 2 diabetes mellitus. BMJ Open. 2019;9(7):e024954. https://doi.org/10.1136/bmjopen-2018-024954
  104. Sportelli C, Urso D, Jenner P, Chaudhuri K. Metformin as a Potential Neuroprotective Agent in Prodromal Parkinson’s Disease — Viewpoint. Front Neurol. 2020;11:Article 556.  https://doi.org/10.3389/fneur.2020.00556
  105. Aroda V, Edelstein S, Goldberg R, et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. The Journal of Clinical Endocrinology & Metabolism. 2016;101(4):1754-1761. https://doi.org/10.1210/jc.2015-3754
  106. Christine C, Auinger P, Saleh N, et al. Relationship of Cerebrospinal Fluid Vitamin B12 Status Markers With Parkinson’s Disease Progression. Movement Disorders. 2020;35(8):1466-1471. https://doi.org/10.1002/mds.28073
  107. Hunter K, Hölscher C. Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis. BMC Neurosci. 2012;13(1):Article 33.  https://doi.org/10.1186/1471-2202-13-33
  108. Yuan Z, Li D, Feng P, et al. A novel GLP-1/GIP dual agonist is more effective than liraglutide in reducing inflammation and enhancing GDNF release in the MPTP mouse model of Parkinson’s disease. Eur J Pharmacol. 2017;812:82-90.  https://doi.org/10.1016/j.ejphar.2017.06.029
  109. Finan B, Ma T, Ottaway N, et al. Unimolecular Dual Incretins Maximize Metabolic Benefits in Rodents, Monkeys, and Humans. Sci Transl Med. 2013;5(209):209ra151-209ra151. https://doi.org/10.1126/scitranslmed.3007218
  110. Ji C, Xue G, Lijun C, et al. A novel dual GLP-1 and GIP receptor agonist is neuroprotective in the MPTP mouse model of Parkinson′s disease by increasing expression of BNDF. Brain Res.2016;1634:1-11.  https://doi.org/10.1016/j.brainres.2015.09.035
  111. Shi L, Zhang Z, Li L, Hölscher C. A novel dual GLP-1/GIP receptor agonist alleviates cognitive decline by re-sensitizing insulin signaling in the Alzheimer icv. STZ rat model. Behav Brain Res. 2017;327:65-74.  https://doi.org/10.1016/j.bbr.2017.03.032

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.