Modulation of glucose uptake and insulin sensitivity in insulin resistant in vitro Alzheimer’s Disease model by vitamin D and E
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1
Department of Biomedical Sciences, Faculty of Medicine and Health sciences, University of Putra Malaysia, Malaysia
Background
Currently, there is a widening recognition that impaired insulin signaling which causes a brain-specific form of diabetes contributes to the pathogenesis of Alzheimer’s Disease (AD). Previous study has reported that high concentration of insulin can alter expression of insulin signal transduction cascade such as insulin receptor (IR), glucose transporter (GLUT4), phosphatidylinositol 3-kinase (PI3K) and glycogen synthase kinase 3 (GSK3) which lead to inhibition of glucose uptake into the cell. Progressive derangements of brain glucose utilization due to insulin insensitivity cause the impairment of glucose homeostasis, hence increasing the oxidative stress which leads to the pathogenesis of AD. Vitamin D has been recognized to have a direct beneficial effect on insulin action by stimulating the expression of insulin receptors. Meanwhile, vitamin E possesses a neuroprotective effect by scavenging oxidative stress effectively. This study aims to elucidate the effect of vitamin D and E in modulating insulin signaling and AD markers in insulin resistant in vitro AD model.
Methods
SK-N-SH (neuroblastoma) was induced with high insulin prior to assess the mRNA expression of insulin signaling markers (IR, GLUT4 and PI3K), AD markers (TAU and GSK3β) and glucose uptake level. Treatment of vitamin D, E and a combination treatment were introduced for 24 hours upon completion of insulin induction.
Results
Improvement of insulin signaling pathway was observed upon treatment of vitamin D alone by significantly increase the level of IR, GLUT4 and PI3K, and glucose uptake level. Reduced expression of both AD markers was observed upon treatment with vitamin D. However, vitamin E and a combination treatment of both vitamins showed insignificant changes in insulin signaling and AD markers.
Conclusion
Vitamin D and E may demonstrate as an agent that slows the progression of Alzheimer Disease caused by insulin resistance in the brain.
Keywords:
Insulin Resistance,
Alzheimer’s disease,
Vitamin E,
Vitamin D,
neurodegenerative
Conference:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019.
Presentation Type:
Poster Presentation
Topic:
Metabolic diseases
Citation:
Ibrahim
N,
Khaza'Ai
H,
Zaulkaffli
A and
Nordin
N
(2019). Modulation of glucose uptake and insulin sensitivity in insulin resistant in vitro Alzheimer’s Disease model by vitamin D and E.
Front. Pharmacol.
Conference Abstract:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”.
doi: 10.3389/conf.fphar.2018.63.00068
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Received:
30 Sep 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Miss. Nafissa Nadia Ibrahim, Department of Biomedical Sciences, Faculty of Medicine and Health sciences, University of Putra Malaysia, Kuala Lumpur, Malaysia, nafissanadia@yahoo.com.my