Altered plasma visfatin levels and insulin resistance in patients with Alzheimer’s disease
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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.
KeywordsVisfatin Alzheimer disease Insulin resistance Dementia
This study was supported by a grant from Qom University of Medical Sciences (Grant number 94579) in/ Qom, Iran.
Compliance with ethical standards
Conflict of interest
There is no conflict of interest for any of the contributing authors. The authors alone are responsible for the content and writing of the paper.
All procedures in this study were in accordance to the ethical principles and the national norms and standards for conducting Medical Research in Iran, which is based on ethical standards of Helsinki declaration. The proposal of this study has been approved by the research ethics committee (approval ID: IR.MUQ.Rec.1394.100), meeting the professional and legal requirements is the sole responsibility of the PI and other project collaborators.
Informed consent was obtained from all participants.
- 5.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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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):615–618Google Scholar
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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):446–452Google Scholar