ArticleClinical and translational medicine2020
Low-glucose-sensitive TRPC6 dysfunction drives hypoglycemia-induced cognitive impairment in diabetes.
Article in Clinical and translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Effect of hypoglycemic events on cognitive function in individuals with type 2 diabetes mellitus: a dose-response meta-analysis.Frontiers in neurology · 2024Pooled it
- Activation of Glucagon-Like Peptide-1 Receptor Ameliorates Cognitive Decline in Type 2 Diabetes Mellitus Through a Metabolism-Independent Pathway.Journal of the American Heart Association · 2021Trial
- Drp1-Dependent Mitochondrial Fission in the Hippocampus Drives Chronic Stress-Induced Depressive-like Behaviors in Mice.International journal of molecular sciences · 2026Article
- Single-Nucleus Transcriptome Reveals Cellular Heterogeneity and Transcriptional Response to Heat Stress in Skeletal Muscle.Journal of cachexia, sarcopenia and muscle · 2026Article
- Hypoglycemia and Alzheimer Disease Risk: The Possible Role of Dasiglucagon.Cellular and molecular neurobiology · 2024Review
- Neuron-targeted overexpression of caveolin-1 alleviates diabetes-associated cognitive dysfunction via regulating mitochondrial fission-mitophagy axis.Cell communication and signaling : CCS · 2023Article
- CaMKK2 as an emerging treatment target for bipolar disorder.Molecular psychiatry · 2023Review
- Dementia in Diabetes: The Role of Hypoglycemia.International journal of molecular sciences · 2023Review
- The Impact of Intermittent Hypoxia on Metabolism and Cognition.International journal of molecular sciences · 2022Review
- Impairment of Mitochondrial Respiration in Metabolic Diseases: An Overview.International journal of molecular sciences · 2022Review
- Recurrent moderate hypoglycemia accelerates the progression of Alzheimer's disease through impairment of the TRPC6/GLUT3 pathway.JCI insight · 2022Article
- Recurrent Hypoglycemia Impaired Vascular Function in Advanced T2DM Rats by Inducing Pyroptosis.Oxidative medicine and cellular longevity · 2022Article
- Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks.International journal of molecular sciences · 2021Article
- Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials.Archives of pharmacal research · 2021Review
- Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke.International journal of molecular sciences · 2021Review
- Low-glucose-sensitive TRPC6 dysfunction drives hypoglycemia-induced cognitive impairment in diabetes.Clinical and translational medicine · 2020Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundRecurrent moderate hypoglycemia (RH), a major adverse effect of hypoglycemic therapy in diabetic patients, is one of the main risk factors for cognitive impairment and dementia. Transient receptor potential canonical channel 6 (TRPC6) is a potential therapeutic target for Alzheimer's disease (AD) and its expression is highly regulated by glucose concentration.
objectiveTo investigate whether RH regulates the expression of TRPC6 in brain and whether TRPC6 dysfunction can drive hypoglycemia-associated cognitive impairment in diabetes, and reveal the underlying mechanism.
methodsHistological staining, in vivo two-photon Ca
resultsHere, we report that the expression of TRPC6 in hippocampus was specifically repressed by RH in streptozocin-induced type 1 diabetic mice, but not in nondiabetic mice. TRPC6 knockout directly leads to neuron loss, neuronal activity, and cognitive function impairment under diabetic condition, the degree of which is similar to that of RH. Activation of TRPC6 with hyperforin substantially improved RH-induced cognitive impairment. Mechanistically, TRPC6 inhibited mitochondrial fission in the hippocampus of diabetic mice undergoing RH episodes by activating adenosine 5'-monophosphate-activated protein kinase, and TRPC6-mediated cytosolic calcium influx was required for this process. Clinically, dysfunction of TRPC6 was closely associated with cognitive impairment in type 2 diabetic patients with RH.
conclusionsOur results indicate that TRPC6 is a critical sensitive cation channel to hypoglycemia and is a promising target to prevent RH-induced cognitive impairment by properly orchestrating the mitochondrial dynamics in diabetic patients.
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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 Socratic graph.