ArticleJCI insight2023
KATP channels are necessary for glucose-dependent increases in amyloid-β and Alzheimer's disease-related pathology.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- KCNQ1 disruption alters human neuronal development through mitochondrial and insulin signalling pathways.Communications biology · 2026Article
- Early microglial response to amyloid plaques drives sleep loss in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Lactate metabolism links reactive microglia, amyloid pathology, and Aβ dynamics.Journal of neuroinflammation · 2026Article
- Tau pathology reprograms glucose metabolism to support cortical hyperexcitability, excitatory/inhibitory imbalance, and sleep loss.NPJ dementia · 2026Article
- Acute high glucose exposure impairs synaptosomal vesicle release activity.Brain research · 2025Article
- The Remarkable Role of Triosephosphate Isomerase in Diabetes Pathophysiology.International journal of molecular sciences · 2025Review
- Impaired insulin receptor function alters psychiatric behaviors without affecting circadian rhythms in a mouse model of Alzheimer's disease.Geriatrics & gerontology international · 2025Article
- ATP-sensitive potassium channels alter glycolytic flux to modulate cortical activity and sleep.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Integrating causal human genetics andFrontiers in molecular biosciences · 2025Article
- Global Burden of Alzheimer's Disease Attributable to High Fasting Plasma Glucose: Epidemiological Trends and Machine Learning Insights.Risk management and healthcare policy · 2025Article
- Exploratory Dual PET imaging of [Bioorganic & medicinal chemistry letters · 2024Article
- Modal Analysis of Cerebrovascular Effects for Digital Health Integration of Neurostimulation Therapies-A Review of Technology Concepts.Brain sciences · 2024Article
- KArhiv za farmaciju · 2024Article
- Ketone bodies mediate alterations in brain energy metabolism and biomarkers of Alzheimer's disease.Frontiers in neuroscience · 2023Review
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
Elevated blood glucose levels, or hyperglycemia, can increase brain excitability and amyloid-β (Aβ) release, offering a mechanistic link between type 2 diabetes and Alzheimer's disease (AD). Since the cellular mechanisms governing this relationship are poorly understood, we explored whether ATP-sensitive potassium (KATP) channels, which couple changes in energy availability with cellular excitability, play a role in AD pathogenesis. First, we demonstrate that KATP channel subunits Kir6.2/KCNJ11 and SUR1/ABCC8 were expressed on excitatory and inhibitory neurons in the human brain, and cortical expression of KCNJ11 and ABCC8 changed with AD pathology in humans and mice. Next, we explored whether eliminating neuronal KATP channel activity uncoupled the relationship between metabolism, excitability, and Aβ pathology in a potentially novel mouse model of cerebral amyloidosis and neuronal KATP channel ablation (i.e., amyloid precursor protein [APP]/PS1 Kir6.2-/- mouse). Using both acute and chronic paradigms, we demonstrate that Kir6.2-KATP channels are metabolic sensors that regulate hyperglycemia-dependent increases in interstitial fluid levels of Aβ, amyloidogenic processing of APP, and amyloid plaque formation, which may be dependent on lactate release. These studies identify a potentially new role for Kir6.2-KATP channels in AD and suggest that pharmacological manipulation of Kir6.2-KATP channels holds therapeutic promise in reducing Aβ pathology in patients with diabetes or prediabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.