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Interlink Between Insulin Resistance and Neurodegeneration with an Update on Current Therapeutic Approaches

[ Vol. 19 , Issue. 3 ]

Author(s):

Subrat Kumar Bhattamisra*, Lee Yuen Shin, Hanis Izzati Binti Mohd Saad, Vikram Rao, Mayuren Candasamy, Manisha Pandey and Hira Choudhury   Pages 174 - 183 ( 10 )

Abstract:


The interlink between diabetes mellitus and neurodegenerative diseases such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) has been identified by several researchers. Patients with Type-2 Diabetes Mellitus (T2DM) are found to be affected with cognitive impairments leading to learning and memory deficit, while patients with Type-1 Diabetes Mellitus (T1DM) showed less severe levels of these impairments in the brain. This review aimed to discuss the connection between insulin with the pathophysiology of neurodegenerative diseases (AD and PD) and the current therapeutic approached mediated through insulin for management of neurodegenerative diseases. An extensive literature search was conducted using keywords “insulin”; “insulin resistance”; “Alzheimer’s disease”; “Parkinson’s disease” in public domains of Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Studies have shown that impaired insulin signaling contributes to the accumulation of amyloid-β, neurofibrillary tangles, tau proteins and α-synuclein in the brain. Whereas, improvement in insulin signaling slows down the progression of cognitive decline. Various therapeutic approaches for altering the insulin function in the brain have been researched. Besides intranasal insulin, other therapeutics like PPAR-γ agonists, neurotrophins, stem cell therapy and insulin-like growth factor-1 are under investigation. Research has shown that insulin insensitivity in T2DM leads to neurodegeneration through mechanisms involving a variety of extracellular, membrane receptor, and intracellular signaling pathway disruptions. Some therapeutics, such as intranasal administration of insulin and neuroactive substances have shown promise but face problems related to genetic background, accessibility to the brain, and invasiveness of the procedures.

Keywords:

Insulin resistance, amyloid β, α-synuclein, tau protein, insulin, neurodegeneration.

Affiliation:

Department of Life Sciences, School of Pharmacy, International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, School of Health Sciences, International Medical University, Bukit Jalil 57000, Kuala Lumpur, School of Health Sciences, International Medical University, Bukit Jalil 57000, Kuala Lumpur, School of Postgraduate Studies, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Department of Life Sciences, School of Pharmacy, International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Bukit Jalil 57000, Kuala Lumpur

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