ArticleJournal of translational medicine2026
FNDC5/irisin ameliorates diabetes-associated cognitive dysfunction via αVβ5-cAMP signaling to regulate oxidative stress, neuroinflammation and synaptic plasticity.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- ERα Agonist Protects Aged Female Mice From Sevoflurane Neurotoxicity via PTEN Nuclear Translocation.CNS neuroscience & therapeutics · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFNDC5/Irisin is a key regulator of cognitive function, but its role in diabetes-associated cognitive decline (DACD) and underlying mechanisms remain unclear. This study aimed to investigate the expression and mechanistic effects of FNDC5/Irisin in DACD.
methodsSTZ-induced diabetic rats were evaluated for cognitive deficits using the Morris water maze. Hippocampal and serum FNDC5/Irisin levels were measured during DACD progression. Hippocampus-specific FNDC5/Irisin overexpression was achieved via an adeno-associated virus. Transcriptomic and untargeted metabolomic analyses were performed to identify potential signaling pathways. In vitro experiments using Fndc5 knockdown and recombinant Irisin further validated the mechanisms.
resultsFNDC5/Irisin was reduced in the hippocampus of diabetic rats, correlating with cognitive impairment. Overexpression restored neuronal structure and improved cognitive performance. Multi-omics integration indicated that FNDC5/Irisin mitigates DACD via modulation of oxidative stress, neuroinflammation, and cAMP signaling. Mechanistically, FNDC5/Irisin suppressed oxidative stressmarked by increased oxidized glutathione, arachidonic acid, 2-hydroxy-dAMP, hydroquinone, and xanthine, and decreased riboflavin and glial activation, regulated inflammatory responses (downregulating pro-inflammatory cytokines IL-1β, TNF-α, IL-6, IFN-γ, and KC/GRO, while upregulating anti-inflammatory cytokines IL-4, IL-10, and IL-13). It also activated cAMP signaling via the integrin αVβ5 receptor, enhancing dendritic complexity, spine density, and synaptic plasticity.
conclusionsThis study demonstrates for the first time that FNDC5/Irisin is a critical modulator of DACD, alleviating cognitive deficits through interplay among oxidative stress, inflammation, and synaptic plasticity. These findings provide novel mechanistic insights and highlight FNDC5/Irisin as a potential therapeutic target for DACD.
Indexed as
Identifiers
What OpenQuestion holds
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.