Cited by 302Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchMetabolism, Diabetes, and Cancer

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Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer’s-like changes

Gupta, Amit, Bisht, Bharti, Dey, Chinmoy Sankar·2011·Neuropharmacology

DOI 10.1016/j.neuropharm.2011.01.033

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Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide. Pharmacological treatments presently available can slow down the progression of symptoms but can not cure the disease. Currently there is widening recognition that AD is closely associated with impaired insulin signaling and glucose metabolism in brain, suggesting it to be a brain-specific form of diabetes and so also termed as "type 3 diabetes". Hence investigating the role of pharmacological agents that could ameliorate neuronal insulin resistance merit attention in AD therapeutics, however the therapeutics for pathophysiological condition like neuronal insulin resistance itself is largely unknown. In the present study we have determined the effect of metformin on neuronal insulin resistance and AD-associated characteristics in an in vitro model of "type 3 diabetes" by differentiating neuronal cell line Neuro-2a under prolonged presence of insulin. We observed that prolonged hyperinsulinemic conditions in addition to generating insulin resistance also led to development of hallmark AD-associated neuropathological changes. Treatment with metformin sensitized the impaired insulin actions and also prevented appearance of molecular and pathological characteristics observed in AD. The results thus demonstrate possible therapeutic efficacy of peripheral insulin-sensitizer drug metformin in AD by its ability to sensitize neuronal insulin resistance. These findings also provide direct evidences linking hyperinsulinemia and AD and suggest a unique opportunity for prevention and treatment of "type 3 diabetes".

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Authors: Gupta, A., Bisht, B., & Dey, C. S.
Affiliations: National Institute of Pharmaceutical Education and Research (IN)
Corresponding author: Dey, Chinmoy Sankar
ORCID: Gupta, Amit
Bisht, Bharti
Dey, Chinmoy Sankar
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2011-05
Volume: 60
Issue: 6
Pages: 910-920
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/j.neuropharm.2011.01.033
OpenAlex: W2001599368
Cited by: 302
References: 61
Citations by year: 2026: 10 · 2025: 11 · 2024: 29 · 2023: 15 · 2022: 26 · 2021: 25 · 2020: 25 · 2019: 19 · 2018: 27 · 2017: 20 · 2016: 22 · 2015: 16 · 2014: 23 · 2013: 16 · 2012: 15
FWCI: 12.44
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuropharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: Department of Science and Technology, Ministry of Science and Technology, India
Council of Scientific and Industrial Research, India
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: metformin, Alzheimer's disease, type 3 diabetes, hyperinsulinemia, insulin signaling, N2a cells, insulin-sensitizing drugs, brain glucose metabolism
MeSH terms: Alzheimer Disease, Animals, Cell Line, Cholinesterases, Diabetes Mellitus, Experimental, Glucose, Hyperinsulinism, Hypoglycemic Agents, Insulin Resistance, Metformin, Neurons, Peptide Fragments, Amyloid beta-Peptides, Phosphatidylinositol 3-Kinases, Mice

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Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer’s-like changes

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