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01-08-2020 | Insulins | Original article

Altered plasma visfatin levels and insulin resistance in patients with Alzheimer’s disease

Authors: Ehsan Sharifipour, Soroush Sharifimoghadam, Navid Hassanzadeh, Negin Ghasemian Mojarad, Abdoreza Ghoreishi, Seyyed Amir Hejazi, Kambiz Rohampour

Published in: Acta Neurologica Belgica | Issue 4/2020

Abstract

Central insulin resistance is involved in the pathophysiology of Alzheimer’s disease (AD). Visfatin (VIS), an adipokine secreted from peripheral adipose tissue, is involved in energy balance and weight control. Besides its metabolic roles, VIS possesses insulin-mimetic, anti-apoptotic, and neuroprotective properties. In this study, we assessed the presence of a correlation between plasma VIS level and insulin resistance or AD. Sixty participants were enrolled in this study; 34 patients with AD and 26 healthy subjects. All subjects underwent comprehensive evaluations including Mini-mental score exam (MMSE) for the diagnosis of dementia. Subjects with MMSE score < 24 were added to the AD group, while healthy subjects should have a MMSE score > 27. Fasting blood sugar (FBS) and insulin levels were measured by enzyme-linked immunosorbent assay. The results indicate a significant elevation in FBS from 103 ± 3.0 to 147 ± 7.6 in AD patients (p ≤ 0.001). Additionally, 71% of AD patients developed insulin resistance, as the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index increased from 2.9 ± 0.5 in healthy subjects to 5.2 ± 0.7 in AD patients (p ≤ 0.05). Body mass index and serum insulin level did not show a significant alteration, but serum VIS levels were significantly (p ≤ 0.01) lower in AD patients (11.15 ± 1.9 ng/ml) in comparison to control group (21.09 ± 2.3 ng/ml). There is a negative correlation between plasma VIS level and the HOMA-IR index (p < 0.05). The results of this study present clear evidence for systemic insulin resistance and decreased serum VIS level in non-obese, non-overweight patients with moderate to severe AD.

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Burns A, Iliffe S (2009) Alzheimer’s disease. BMJ 338:b158CrossRef

Li J, Cesari M, Liu F, Dong B, Vellas B (2017) Effects of diabetes mellitus on cognitive decline in patients with Alzheimer disease: a systematic review. Can J Diabetes 41(1):114–119. https://doi.org/10.1016/j.jcjd.2016.07.003 CrossRefPubMed

Schrijvers EM, Witteman JC, Sijbrands EJ, Hofman A, Koudstaal PJ, Breteler MM (2010) Insulin metabolism and the risk of Alzheimer disease: the Rotterdam Study. Neurology 75(22):1982–1987. https://doi.org/10.1212/WNL.0b013e3181ffe4f6 CrossRefPubMedPubMedCentral

Dudek H, Datta SR, Franke TF, Birnbaum MJ, Yao R, Cooper GM, Segal RA, Kaplan DR, Greenberg ME (1997) Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 275(5300):661–665CrossRef

Willette AA, Bendlin BB, Starks EJ, Birdsill AC, Johnson SC, Christian BT, Okonkwo OC, La Rue A, Hermann BP, Koscik RL, Jonaitis EM, Sager MA, Asthana S (2015) Association of insulin resistance with cerebral glucose uptake in late middle-aged adults at risk for Alzheimer disease. JAMA Neurol 72(9):1013–1020. https://doi.org/10.1001/jamaneurol.2015.0613 CrossRefPubMedPubMedCentral

Schubert M, Brazil DP, Burks DJ, Kushner JA, Ye J, Flint CL, Farhang-Fallah J, Dikkes P, Warot XM, Rio C, Corfas G, White MF (2003) Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation. J Neurosci 23(18):7084–7092CrossRef

de la Monte SM (2009) Insulin resistance and Alzheimer’s disease. BMB Rep 42(8):475–481CrossRef

Arnoldussen IA, Kiliaan AJ, Gustafson DR (2014) Obesity and dementia: adipokines interact with the brain. Eur Neuropsychopharmacol 24(12):1982–1999. https://doi.org/10.1016/j.euroneuro.2014.03.002 CrossRefPubMedPubMedCentral

Kiliaan AJ, Arnoldussen IA, Gustafson DR (2014) Adipokines: a link between obesity and dementia? Lancet Neurol 13(9):913–923. https://doi.org/10.1016/S1474-4422(14)70085-7 CrossRefPubMedPubMedCentral

10.

Balistreri CR, Caruso C, Candore G (2010) The role of adipose tissue and adipokines in obesity-related inflammatory diseases. Mediat Inflamm 2010:802078. https://doi.org/10.1155/2010/802078 CrossRef

11.

Holden KF, Lindquist K, Tylavsky FA, Rosano C, Harris TB, Yaffe K, study HA (2009) Serum leptin level and cognition in the elderly: findings from the Health ABC Study. Neurobiol Aging 30(9):1483–1489. https://doi.org/10.1016/j.neurobiolaging.2007.11.024 CrossRefPubMed

12.

Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I (2005) Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307(5708):426–430. https://doi.org/10.1126/science.1097243 CrossRefPubMed

13.

Tu TH, Nam-Goong IS, Lee J, Yang S, Kim JG (2017) Visfatin triggers anorexia and body weight loss through regulating the inflammatory response in the hypothalamic microglia. Mediat Inflamm 2017:1958947. https://doi.org/10.1155/2017/1958947 CrossRef

14.

Erfani S, Khaksari M, Oryan S, Shamsaei N, Aboutaleb N, Nikbakht F (2015) Nampt/PBEF/visfatin exerts neuroprotective effects against ischemia/reperfusion injury via modulation of Bax/Bcl-2 ratio and prevention of caspase-3 activation. J Mol Neurosci 56(1):237–243. https://doi.org/10.1007/s12031-014-0486-1 CrossRefPubMed

15.

Wang P, Xu TY, Guan YF, Tian WW, Viollet B, Rui YC, Zhai QW, Su DF, Miao CY (2011) Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate-activated kinase pathway. Ann Neurol 69(2):360–374. https://doi.org/10.1002/ana.22236 CrossRefPubMed

16.

Skop V, Kontrová K, Zídek V, Pravenec M, Kazdová L, Mikulík K, Sajdok J, Zídková J (2010) Autocrine effects of visfatin on hepatocyte sensitivity to insulin action. Physiol Res 59(4):615–618PubMed

17.

Jack CR, Albert MS, Knopman DS, McKhann GM, Sperling RA, Carrillo MC, Thies B, Phelps CH (2011) Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3):257–262. https://doi.org/10.1016/j.jalz.2011.03.004 CrossRefPubMedPubMedCentral

18.

Une K, Takei YA, Tomita N, Asamura T, Ohrui T, Furukawa K, Arai H (2011) Adiponectin in plasma and cerebrospinal fluid in MCI and Alzheimer’s disease. Eur J Neurol 18(7):1006–1009. https://doi.org/10.1111/j.1468-1331.2010.03194.x CrossRefPubMed

19.

Hermans MP, Levy JC, Morris RJ, Turner RC (1999) Comparison of insulin sensitivity tests across a range of glucose tolerance from normal to diabetes. Diabetologia 42(6):678–687. https://doi.org/10.1007/s001250051215 CrossRefPubMed

20.

De Felice FG, Lourenco MV, Ferreira ST (2014) How does brain insulin resistance develop in Alzheimer’s disease? Alzheimers Dement 10(1 Suppl):S26–S32. https://doi.org/10.1016/j.jalz.2013.12.004 CrossRefPubMed

21.

Wellen KE, Hotamisligil GS (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Investig 112(12):1785–1788. https://doi.org/10.1172/JCI20514 CrossRefPubMed

22.

Kitagawa K, Miwa K, Okazaki S, Sakaguchi M, Mochizuki H (2016) Serum high-molecular-weight adiponectin level and incident dementia in patients with vascular risk factors. Eur J Neurol 23(3):641–647. https://doi.org/10.1111/ene.12915 CrossRefPubMed

23.

Teixeira AL, Diniz BS, Campos AC, Miranda AS, Rocha NP, Talib LL, Gattaz WF, Forlenza OV (2013) Decreased levels of circulating adiponectin in mild cognitive impairment and Alzheimer’s disease. Neuromolecular Med 15(1):115–121. https://doi.org/10.1007/s12017-012-8201-2 CrossRefPubMed

24.

Bednarska-Makaruk M, Graban A, Wiśniewska A, Łojkowska W, Bochyńska A, Gugała-Iwaniuk M, Sławińska K, Ługowska A, Ryglewicz D, Wehr H (2017) Association of adiponectin, leptin and resistin with inflammatory markers and obesity in dementia. Biogerontology 18(4):561–580. https://doi.org/10.1007/s10522-017-9701-0 CrossRefPubMedPubMedCentral

25.

Gorospe EC, Dave JK (2007) The risk of dementia with increased body mass index. Age Ageing 36(1):23–29. https://doi.org/10.1093/ageing/afl123 CrossRefPubMed

26.

Owczarek AJ, Olszanecka-Glinianowicz M, Kocełak P, Bożentowicz-Wikarek M, Brzozowska A, Mossakowska M, Puzianowska-Kuźnicka M, Grodzicki T, Więcek A, Chudek J (2016) The relationship between circulating visfatin/nicotinamide phosphoribosyltransferase, obesity, inflammation and lipids profile in elderly population, determined by structural equation modeling. Scand J Clin Lab Investig 76(8):632–640. https://doi.org/10.1080/00365513.2016.1230884 CrossRef

27.

Tabassum A, Mahboob T (2018) Role of peroxisome proliferator-activated receptor-gamma activation on visfatin, advanced glycation end products, and renal oxidative stress in obesity-induced type 2 diabetes mellitus. Hum Exp Toxicol. https://doi.org/10.1177/0960327118757588 CrossRefPubMed

28.

Liang Z, Wu Y, Xu J, Fang Q, Chen D (2016) Correlations of serum visfatin and metabolisms of glucose and lipid in women with gestational diabetes mellitus. J Diabetes Investig 7(2):247–252. https://doi.org/10.1111/jdi.12385 CrossRefPubMed

29.

Kazem YM, Shebini SM, Moaty MI, Fouad S, Tapozada ST (2015) Sleep deficiency is a modifiable risk factor for obesity and cognitive impairment and associated with elevated visfatin. Open Access Maced J Med Sci 3(2):315–321. https://doi.org/10.3889/oamjms.2015.063 CrossRefPubMedPubMedCentral

30.

Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, Rademakers R, Vandenberghe R, Dermaut B, Martin JJ, van Duijn C, Peeters K, Sciot R, Santens P, De Pooter T, Mattheijssens M, Van den Broeck M, Cuijt I, Vennekens K, De Deyn PP, Kumar-Singh S, Van Broeckhoven C (2006) Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442(7105):920–924. https://doi.org/10.1038/nature05017 CrossRefPubMed

31.

Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, Snowden J, Adamson J, Sadovnick AD, Rollinson S, Cannon A, Dwosh E, Neary D, Melquist S, Richardson A, Dickson D, Berger Z, Eriksen J, Robinson T, Zehr C, Dickey CA, Crook R, McGowan E, Mann D, Boeve B, Feldman H, Hutton M (2006) Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442(7105):916–919. https://doi.org/10.1038/nature05016 CrossRefPubMed

32.

Lu YC, Hsu CC, Yu TH, Wang CP, Lu LF, Hung WC, Chiu CA, Chung FM, Lee YJ, Tsai IT (2013) Association between visfatin levels and coronary artery disease in patients with chronic kidney disease. Iran J Kidney Dis 7(6):446–452PubMed

33.

Mazrooie R, Rohampour K, Zamani M, Hosseinmardi N, Zeraati M (2017) Intracerebroventricular administration of adiponectin attenuates streptozotocin-induced memory impairment in rats. Physiol Int 104(2):150–157. https://doi.org/10.1556/2060.104.2017.1.4 CrossRefPubMed

34.

Pousti F, Ahmadi R, Mirahmadi F, Hosseinmardi N, Rohampour K (2018) Adiponectin modulates synaptic plasticity in hippocampal dentate gyrus. Neurosci Lett 662:227–232. https://doi.org/10.1016/j.neulet.2017.10.042 CrossRefPubMed

35.

Kang YS, Bae MK, Kim JY, Jeong JW, Yun I, Jang HO, Bae SK (2011) Visfatin induces neurite outgrowth in PC12 cells via ERK1/2 signaling pathway. Neurosci Lett 504(2):121–126. https://doi.org/10.1016/j.neulet.2011.09.014 CrossRefPubMed

36.

Zhang W, Xie Y, Wang T, Bi J, Li H, Zhang LQ, Ye SQ, Ding S (2010) Neuronal protective role of PBEF in a mouse model of cerebral ischemia. J Cereb Blood Flow Metab 30(12):1962–1971. https://doi.org/10.1038/jcbfm.2010.71 CrossRefPubMedPubMedCentral

Title: Altered plasma visfatin levels and insulin resistance in patients with Alzheimer’s disease
Authors: Ehsan Sharifipour
Soroush Sharifimoghadam
Navid Hassanzadeh
Negin Ghasemian Mojarad
Abdoreza Ghoreishi
Seyyed Amir Hejazi
Kambiz Rohampour
Publication date: 01-08-2020
Publisher: Springer International Publishing
Keywords: Insulins
Alzheimer's Disease
Dementia
Alzheimer's Disease
Dementia
Insulins
Published in: Acta Neurologica Belgica / Issue 4/2020
Print ISSN: 0300-9009
Electronic ISSN: 2240-2993
DOI: https://doi.org/10.1007/s13760-019-01084-9

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Altered plasma visfatin levels and insulin resistance in patients with Alzheimer’s disease

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