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Diabetes mellitus and Alzheimer's disease: GSK-3β as a potential link
Abstract
It is well known that Alzheimer's disease (AD) is closely related to diabetes mellitus (DM), and AD is also regarded as Type 3 diabetes (T3D). However, the exact link between AD and DM is still unclear. Recently, more and more evidence has shown that glycogen synthase kinase-3β (GSK-3β) may be the potential link between DM and AD. In DM, GSK-3β is the crucial enzyme of glycogen synthesis, which plays a key role in regulating blood glucose. More importantly, GSK-3β is one of the key factors leading to insulin deficiency and insulin resistance, and insulin resistance is an important hallmark of the occurrence and development of DM. In AD, GSK-3β plays an important role in hyperphosphorylation of microtubule-associated protein tau (tau), which is one of the pathological features in AD. GSK-3β is one of the important kinases of tau phosphorylation and is involved in the insulin/phosphoinositide 3-kinase/protein kinase B (insulin/PI3K/Akt) signaling pathway. Dysfunction of the insulin/PI3K/Akt signaling pathway, which regulates glucose metabolism in the brain, can lead to tau hyperphosphorylation in the brain of AD patents. Additionally, insulin resistance in DM may cause β-amyloid (Aβ) deposition, which will be cleared by tau, but excessive phosphorylation of tau will further aggravate the neurotoxicity; then damage the brain and affect the cognitive function. GSK-3β is considered as a common kinase in insulin signaling transduction and tau protein phosphorylation, so we have reasons to believe that GSK-3β is a potential link between DM and AD.
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“Impaired insulin secretion is multifactorial, the exact mechanism is still unclear, but commonly develops from glucose toxicity, lipid toxicity, immunoinflammatory response, and oxidative stress, leading to the dysfunction of islet β cells (72).”
From Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments (2020) · cites this paper as [72]
In the citing paper
“When the insulin signaling pathway fails, the expression of GSK3β improves, which reduces the insulin sensitivity and increases the levels of blood glucose, thus subsequently leading to T2D (72, 96, 97).”
From Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments (2020) · cites this paper as [72]
In the citing paper
“In addition, the impairment of insulin signaling induces an increased activation of GSK-3β, which phosphorylates Tau, hence leading to Tau hyperphosphorylation (Hong and Lee, 1997; Planel et al., 2007; Zhang et al., 2018; Wei et al., 2021).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Zhang et al., 2018
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Metadata
- Authors
- Zhang, Y., Huang, N.-Q., Yan, F., Jin, H., Zhou, S.-Y., Shi, J.-S., & Jin, F.
- Affiliations
- Zunyi Medical University (CN)
- Corresponding author
- Jin, Hai
- Jin, Feng
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 339
- Pages
- 57-65
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2770586248
- Cited by
- 301
- References
- 130
- Citations by year
- 2026: 28 · 2025: 38 · 2024: 45 · 2023: 48 · 2022: 42 · 2021: 38 · 2020: 37 · 2019: 14 · 2018: 10
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81660599, 81360311, 81460548)
- Postgraduate Education Foundation of Guizhou Province (KYJJ2017008)
- Zunyi Medical University Funds (2013F-686, F-738)
- 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 › Cell Biology › Aldose Reductase and Taurine
- Keywords
- diabetes mellitus, Alzheimer's disease, glycogen synthase kinase-3β, type 3 diabetes, insulin resistance, tau hyperphosphorylation, amyloid-beta deposition, glycogen synthesis, neurotoxicity
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Alzheimer Disease, Animals, Diabetes Mellitus, Humans, Insulin, Amyloid beta-Peptides, tau Proteins
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