ArticleJournal of neuroinflammation2024
Inhibition of ANGPTL8 protects against diabetes-associated cognitive dysfunction by reducing synaptic loss via the PirB signaling pathway.
Article in Journal of neuroinflammation, 2024. 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.
- An ANGPTL8-AKT2-mTOR Axis Drives Adipose Senescence and Aging-Related Functional Decline.Aging cell · 2026Article
- Persistent PirB cleavage drives Golgi-directed trafficking deficits underlying neurodegeneration.Translational neurodegeneration · 2026Article
- Angiopoietin-like Proteins 4 and 8 in Diabetic Complications: Associations with Neuropathy and Metabolic Parameters in Type 2 Diabetes.Journal of clinical medicine · 2026Article
- ANGPTL8 accelerates bone loss in diabetic mice by promoting osteoclastic differentiation and inhibiting osteoblastic differentiation through AMPK pathway-mediated metabolic reprogramming.Cellular and molecular life sciences : CMLS · 2026Article
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- ANGPTL8 links refeeding to monocyte dynamics and metabolic inflammation via the CCL5-CCR5 axis.JCI insight · 2026Article
- Association between serum ANGPLT8 levels and atherogenic index of plasma in Chinese patients with type 2 diabetes mellitus.Frontiers in cardiovascular medicine · 2026Article
- Comorbidity Between Mood Disorders and Chronic Somatic Diseases, With a Focus on Cardiometabolic Disease, and Its Mechanistic Crosstalk.Depression and anxiety · 2026Review
- Epigenetic Regulation of DAPK1 and Netrin-1 Drives Diabetic Encephalopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Liver-specific expression of ANGPTL8 promotes Alzheimer's disease progression through activating microglial pyroptosis.Journal of neuroinflammation · 2025Article
- Photo-Biomodulation of the Hippocampus Using Near-Infrared Laser to Enhance Cognitive Function in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Brain-acting hepatokines: its impact on energy balance and metabolism.Frontiers in neuroscience · 2025Review
- Article
- Antin-diabetic cognitive dysfunction effects and underpinning mechanisms of phytogenic bioactive peptides: a review.Frontiers in nutrition · 2024Review
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Authors and funding
21 authors.
Funding
Abstract
backgroundType 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system.
methodsThe levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB
resultsHere, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB
conclusionTaken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.
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