ArticleAging2019
Chronic hyperglycemia regulates microglia polarization through ERK5.
Article in Aging, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- HMC3 revealed: how much do these "Microglia" really tell us?Frontiers in immunology · 2026Review
- Cellular Abnormalities Induced by High Glucose in Mixed Glial Cultures Are Maintained, Although Glucose Returns to Normal Levels.Brain sciences · 2025Article
- Enhanced M2 Polarization of Retinal Microglia in Streptozotocin-Induced Diabetic Mice upon Autoimmune Stimulation.Biomedicines · 2025Article
- The Association of Glycemic Gap with Cognitive Function After Ischemic Stroke or Transient Ischemic Attack.Neuropsychiatric disease and treatment · 2025Article
- Exercise Promotes Hippocampal Neurogenesis in T2DM Mice via Irisin/TLR4/MyD88/NF-κB-Mediated Neuroinflammation Pathway.Biology · 2024Article
- Role of microglia/macrophage polarisation in intraocular diseases (Review).International journal of molecular medicine · 2024Review
- Glial cell alterations in diabetes-induced neurodegeneration.Cellular and molecular life sciences : CMLS · 2024Review
- Cell and molecular targeted therapies for diabetic retinopathy.Frontiers in endocrinology · 2024Review
- Exosomal miR-let-7c-5p is involved in the cognitive function of type 2 diabetes mellitus patients by interleukin 10: A cross-sectional study.Journal of diabetes · 2023Article
- Metabolic Profile of Alzheimer's Disease: Is 10-Hydroxy-2-decenoic Acid a Pertinent Metabolic Adjuster?Metabolites · 2023Review
- Association between diabetes mellitus and post-stroke cognitive impairment.Journal of diabetes investigation · 2023Review
- Macrophage/microglia polarization for the treatment of diabetic retinopathy.Frontiers in endocrinology · 2023Review
- Contribution of hyperglycemia-induced changes in microglia to Alzheimer's disease pathology.Pharmacological reports : PR · 2022Review
- 1-L Transcription in Alzheimer's Disease.Current issues in molecular biology · 2022Article
- Sesamin protects against neurotoxicity via inhibition of microglial activation under high glucose circumstances through modulating p38 and JNK signaling pathways.Scientific reports · 2022Article
- Characterization of an Immortalized Human Microglial Cell Line as a Tool for the Study of Diabetic Retinopathy.International journal of molecular sciences · 2022Article
- New models of Parkinson's like neuroinflammation in human microglia clone 3: Activation profiles induced by INF-γ plus high glucose and mitochondrial inhibitors.Frontiers in cellular neuroscience · 2022Article
- Hypothalamic inflammation in metabolic disorders and aging.Cellular and molecular life sciences : CMLS · 2021Review
- Regulation of the Fructose Transporter GeneInternational journal of molecular sciences · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic patients are prone to developing Alzheimer's disease (AD), in which microglia play a critical role. However, the direct effect of high glucose (HG) on microglia and the role of extracellular-signal-regulated kinase 5 (ERK5) signaling in this interaction have not been examined before. Here, these questions were addressed in microglia cultured in HG versus normal glucose (NG) conditions. Initially, HG induced microglial differentiation into the M2a phenotype with concomitant ERK5 activation. However, longer exposure to HG further induced differentiation of microglia into the M2b-like phenotype, followed by the M1-like subtype, concomitant with a gradual loss of ERK5 activation. BIX021895, a specific inhibitor of ERK5 activation, prevented M2a- differentiation of microglia, but induced earlier M2b-like polarization followed by M1-like polarization. Transfection of microglia with a sustained activated form of MEK5 (MEK5DD) prolonged the duration of the M2a phenotype, and prevented later differentiation into the M2b/M1 subtype. Conditioned media from the M2a-polarized microglia reduced neuronal cell apoptosis in hypoxic condition, while media from M2b-like or M1-like microglia enhanced apoptosis. Together, our data suggest that chronic hyperglycemia may induce a gradual alteration of microglia polarization into an increasingly proinflammatory subtype, which could be suppressed by sustained activation of ERK5 signaling.
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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.