Features of molecule expression markers of insulin resistance in experimental Alzheimer’s disease

Gorina Ya.V.; Komleva Yu.K.; Lopatina O.L.; Volkova V.V.; Gersog G.E.; Popova N.N.; Salmina A.B.

doi:https://doi.org/10.14341/probl201561443-48

Gorina Ya.V.

Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Komleva Yu.K.

Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Lopatina O.L.

Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Volkova V.V.

Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Gersog G.E.

Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Popova N.N.

Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Salmina A.B.

Kafedra biologicheskoĭ khimii s kursami meditsinskoĭ farmatsevticheskoĭ i toksikologicheskoĭ khimii Krasnoiarskogo gosudarstvennogo meditsinskogo universiteta im. prof. V.F. Voĭno-Iasenetskogo, NII molekuliarnoĭ meditsiny i patobiokhimii, Krasnoiarsk

Features of molecule expression markers of insulin resistance in experimental Alzheimer’s disease

Authors:

Gorina Ya.V., Komleva Yu.K., Lopatina O.L., Volkova V.V., Gersog G.E., Popova N.N., Salmina A.B.

More about the authors

Journal: Problems of Endocrinology. 2015;61(4): 43‑48

DOI: 10.14341/probl201561443-48

Read: 742 times

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Gorina YaV, Komleva YuK, Lopatina OL, Volkova VV, Gersog GE, Popova NN, Salmina AB. Features of molecule expression markers of insulin resistance in experimental Alzheimer’s disease. Problems of Endocrinology. 2015;61(4):43‑48. (In Russ.)
https://doi.org/10.14341/probl201561443-48

Использование инфографики авторами научных работ

Close metadata

Recommended articles:

Surgical treatment of macromastia in benign breast dysplasia and comorbidities. Plastic Surgery and Aesthetic Medicine. 2024;(4-2):5-13

Objective structural and functional monitoring of polypeptide retinal neuroprotective therapy in diabetic retinopathy. Russian Annals of Ophthalmology. 2024;(5):97-104

A pilot study of associations of markers of glial and neuronal degeneration with executive functions in alcohol use disorders. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(10):74-79

Motor behavior in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mice model of Parkinson’s disease treated with recombinant spidroin rS1/9 microgel. Molecular Genetics, Microbiology and Virology. 2024;(4):12-17

Effectiveness of using preventive and personalized technologies for obesity correction. Problems of Balneology, Physiotherapy and Exercise Therapy. 2024;(6-2):80-90

Modern aspects of gestational diabetes mellitus: definition, risk factors. Russian Bulletin of Obstetrician-Gynecologist. 2025;(2):35-41

A comprehensive study of Alzheimer’s disease biomarkers in plasma and cerebrospinal fluid. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(4-2):43-53

Prospects for treating Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(4-2):54-60

Triglycerides-Glucose Index as an integral biomarker of insulin resistance and cardiovascular diseases. Russian Journal of Preventive Medicine. 2025;(5):124-129

Drinking mineral water for progressive resistance to insulin. Regenerative Biotechnologies, Preventive, Digital and Predictive Medicine. 2025;(2):24-30

Abstract:

Alzheimer’s Disease (AD) is characterized by a significant loss of neurons and synapses, especially in the hippocampus and cortex, the extracellular β-amyloid accumulation and formation of neurofibrillary tangles. Insulin resistance plays important role in neurodegeneration and cognitive disorders in the central nervous system, especially AD. However, the cellular and molecular mechanisms that connect insulin resistance and Alzheimer’s pathogenesis remain largely unexplained. Therefore, great importance is the identification of molecular markers that allow to define new approaches to targeted pharmacological correction of neurodegeneration. This article describes the study of the expression of molecular markers, namely, IRAP, GLUT4, and IL-18 in different brain regions (hippocampus, olfactory bulb) rats with experimental AD.

Keywords:

molecular markers

insulin resistance

neurodegeneration

insulin-regulated aminopeptidase

GLUT4

IL-18

Authors:

Gorina Ya.V.

Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Komleva Yu.K.

Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Lopatina O.L.

Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Volkova V.V.

Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Gersog G.E.

Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Popova N.N.

Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Salmina A.B.

Close metadata

References:

Prince M, Bryce R, Albanese E, et al. The global prevalence of dementia: A systematic review and metaanalysis.Alzheimer’s & Dementia. 2013;9(1):63-75.e62. doi: 10.1016/j.jalz.2012.11.007.
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia. 2011;7(3):263-269. doi: 10.1016/j.jalz.2011.03.005.
Han W, Li C. Linking type 2 diabetes and Alzheimer’s disease. Proceedings of the National Academy of Sciences.2010;107(15):6557-6558. doi: 10.1073/pnas.1002555107.
Vos SJB, Verhey F, Frölich L, et al. Prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage. Brain. 2015;138(5):1327-1338. doi: 10.1093/brain/awv029.
Kim B, Feldman EL. Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome. Exp Mol Med. 2015;47(3):e149. doi: 10.1038/emm.2015.3.
Gorina YV, Salmina AB, Kuvacheva NV, et al. Static mutations in the pathogenesis of spinocerebellar ataxias: from particular to general (Report III). Siberian medical review. 2014;(4):11-19. (In Russ.)
Cai Z, Xiao M, Chang L, Yan L-J. Role of insulin resistance in Alzheimer’s disease. Metab Brain Dis.2014;30(4):839-851. doi: 10.1007/s11011-014-9631-3.
Liu C, Cui G, Zhu M, et al. Neuroinflammation in Alzheimer’s disease: chemokines produced by astrocytes and chemokine receptors. Int J Clin Exp Pathol. 2014;7(12):8342-8355.
Spielman LJ, Little JP, Klegeris A. Inflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration. J Neuroimmunol. 2014;273(1-2):8-21. doi: 10.1016/j.jneuroim.2014.06.004.
Singhal G, Jaehne EJ, Corrigan F, et al. Inflammasomes in neuroinflammation and changes in brain function: a focused review. Front Neurosci. 2014;8. doi: 10.3389/fnins.2014.00315.
Zhang Q-Y, Pan Y, Wang R, et al. Quercetin inhibits AMPK/TXNIP activation and reduces inflammatory lesions to improve insulin signaling defect in the hypothalamus of high fructose-fed rats. The Journal of Nutritional Biochemistry.2014;25(4):420-428. doi: 10.1016/j.jnutbio.2013.11.014.
Chen Z, Zhong C. Decoding Alzheimer’s disease from perturbed cerebral glucose metabolism: Implications for diagnostic and therapeutic strategies. Prog Neurobiol. 2013;108:21-43. doi: 10.1016/j.pneurobio.2013.06.004.
Chai S, Yeatman HR, Parker MW, et al. Development of cognitive enhancers based on inhibition of insulin-regulated aminopeptidase. BMC Neurosci. 2008;9(Suppl 2):S14. doi: 10.1186/1471-2202-9-s2-s14.
Hermans SJ, Ascher DB, Hancock NC, et al. Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides. Protein Sci. 2015;24(2):190-199. doi: 10.1002/pro.2604.
Yeatman H, Albiston A, Chai S. Insulin-regulated aminopeptidase in astrocytes: Role in Alzheimer’s disease? Alzheimer’s & Dementia. 2011;7(4):S668. doi: 10.1016/j.jalz.2011.05.1922.
Albiston AL, Yeatman HR, Pham V, et al. Distinct distribution of GLUT4 and insulin regulated aminopeptidase in the mouse kidney. Regul Pept. 2011;166(1-3):83-89. doi: 10.1016/j.regpep.2010.09.003.
Li X, Yuan H-f, Quan Q-k, et al. Scavenging effect of Naoerkang (???) on amyloid beta-peptide deposition in the hippocampus in a rat model of Alzheimer’s disease. Chin J Integr Med. 2011;17(11):847-853. doi: 10.1007/s11655-011-0896-7.
Sipos E, Kurunczi A, Kasza Á, et al. β-Amyloid pathology in the entorhinal cortex of rats induces memory deficits: Implications for Alzheimer’s disease. Neuroscience. 2007;147(1):28-36. doi: 10.1016/j.neuroscience.2007.04.011.
Encinas JM, Enikolopov G. Identifying and Quantitating Neural Stem and Progenitor Cells in the Adult Brain. 2008;85:243-272. doi: 10.1016/s0091-679x(08)85011-x.
Mabrouk RR, Mohamed HG, El-Kabarity RH. IL-18, An Indicator of Insulin Resistance? Proc Nutr Soc.2013;72(OCE1). doi: 10.1017/s0029665113000943.
Sutinen EM, Pirttilä T, Anderson G, et al. Pro-inflammatory interleukin-18 increases Alzheimer’s disease-associated amyloid-β production in human neuron-like cells. J Neuroinflammation. 2012;9(1):199. doi: 10.1186/1742-2094-9-199.
De La Monte SM. Insulin resistance and Alzheimer’s disease. BMB Reports. 2009;42(8):475-481. doi: 10.5483/bmbrep.2009.42.8.475.
Leguisamo NM, Lehnen AM, Machado UF, et al. GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome. Cardiovasc Diabetol. 2012;11(1):100. doi: 10.1186/1475-2840-11-100.
Keller SR, Davis AC, Clairmont KB. Mice Deficient in the Insulin-regulated Membrane Aminopeptidase Show Substantial Decreases in Glucose Transporter GLUT4 Levels but Maintain Normal Glucose Homeostasis. J Biol Chem.2002;277(20):17677-17686. doi: 10.1074/jbc.m202037200.
Heneka M, Obanion M. Inflammatory processes in Alzheimer’s disease. J Neuroimmunol. 2007;184(1-2):69-91. doi: 10.1016/j.jneuroim.2006.11.017.
Wyss-Coray T, Rogers J. Inflammation in Alzheimer Disease--A Brief Review of the Basic Science and Clinical Literature. Cold Spring Harb Perspect Med. 2011;2(1):a006346-a006346. doi: 10.1101/cshperspect.a006346.
Griffin WST. Neuroinflammatory Cytokine Signaling and Alzheimer’s Disease. N Engl J Med. 2013;368(8):770-771. doi: 10.1056/nejmcibr1214546.
Griffin RJ, Moloney A, Kelliher M, et al. Activation of Akt/PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer’s disease pathology. J Neurochem. 2005;93(1):105-117. doi: 10.1111/j.1471-4159.2004.02949.x.
Ojala J, Alafuzoff I, Herukka S-K, et al. Expression of interleukin-18 is increased in the brains of Alzheimer’s disease patients. Neurobiol Aging. 2009;30(2):198-209. doi: 10.1016/j.neurobiolaging.2007.06.006.
Ojala JO, Sutinen EM, Salminen A, Pirttilä T. Interleukin-18 increases expression of kinases involved in tau phosphorylation in SH-SY5Y neuroblastoma cells. J Neuroimmunol. 2008;205(1-2):86-93. doi: 10.1016/j.jneuroim.2008.09.012.
Pickering M, O’Connor JJ. Pro-inflammatory cytokines and their effects in the dentate gyrus. 2007;163:339-354. doi: 10.1016/s0079-6123(07)63020-9.
Teune L, Strijkert F, Renken R, et al. The Alzheimer’s Disease-Related Glucose Metabolic Brain Pattern. Curr Alzheimer Res. 2014;11(8):725-732. doi: 10.2174/156720501108140910114230.
Emmanuel Y, Cochlin LE, Tyler DJ, et al. Human hippocampal energy metabolism is impaired during cognitive activity in a lipid infusion model of insulin resistance. Brain and Behavior.2013;3(2):134-144. doi: 10.1002/brb3.124.
Albiston AL, Diwakarla S, Fernando RN, et al. Identification and development of specific inhibitors for insulin-regulated aminopeptidase as a new class of cognitive enhancers. Br J Pharmacol. 2011;164(1):37-47. doi: 10.1111/j.1476-5381.2011.01402.x.
Fernando RN, Larm J, Albiston AL, Chai SY. Distribution and cellular localization of insulin-regulated aminopeptidase in the rat central nervous system. The Journal of Comparative Neurology. 2005;487(4):372-390. doi: 10.1002/cne.20585.
Fernando RN, Albiston AL, Chai SY. The insulin-regulated aminopeptidase IRAP is colocalised with GLUT4 in the mouse hippocampus - potential role in modulation of glucose uptake in neurones? Eur J Neurosci. 2008;28(3):588-598. doi: 10.1111/j.1460-9568.2008.06347.x.
Yeh T-Yin J, Sbodio Juan I, Tsun Z-Y, et al. Insulin-stimulated exocytosis of GLUT4 is enhanced by IRAP and its partner tankyrase. Biochem J. 2007;402(2):279-290. doi: 10.1042/bj20060793.
Keller SR. The insulin-regulated aminopeptidase: a companion and regulator of GLUT4. Front Biosci. 2003;8(1-3):s410. doi: 10.2741/1078.
Stockli J, Fazakerley DJ, James DE. GLUT4 exocytosis. J Cell Sci. 2012;124(24):4147-4159. doi: 10.1242/jcs.097063.
Lim C-Y, Bi X, Wu D, et al. Tropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4 exocytosis through cortical actin remodeling. Nature Communications. 2015;6:5951. doi: 10.1038/ncomms6951.