SynthesisFrontiers in physiology2025
Orexinergic pathway as a potential therapeutic candidate for the modulation of glucose homeostasis.
Synthesis in Frontiers in physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 6 of them syntheses that pooled it.
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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.
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Who cites it
8 citing papers in PubMed, 6 syntheses or guidelines pooled it.
- Utero-placental calcium and magnesium ion channels: A systematic review of obstetric implications of their alterations.Channels (Austin, Tex.) · 2026Pooled it
- Protein sorting and proteostasis mechanisms in CFTR-related exocrine pancreas dysfunction: A systematic narrative review.Channels (Austin, Tex.) · 2026Pooled it
- Melatonin as a protector against endocrine disruption across tissues: A systematic review.Physiological reports · 2026Pooled it
- Physiological significance of autocrine orexinergic signaling in extra-hypothalamic tissues.Physiological reports · 2026Pooled it
- Genetic aetiology of global developmental delay and intellectual disability in Africa: a scoping review.Frontiers in genetics · 2026Pooled it
- Pooled it
- The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.Brain sciences · 2026Review
- Gastric Proton Pumpopathy Associated with Protein Sorting Machinery: A Narrative Review.Clinical and experimental gastroenterology · 2026Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Glucose homeostasis is regulated by both central and peripheral systems to maintain metabolic stability during periods of feeding, fasting, and stress. Orexins A and B, hypothalamic neuropeptides traditionally associated with arousal and feeding behavior, are increasingly recognized for their pivotal role in glucose homeostasis via neural and endocrine mechanisms. This review synthesizes the available data orexinergic-glucose pathway. Method: Following PRISMA guidelines, a systematic search of PubMed and Wiley Online Library identified original studies (between January 1999 and May 2025) examining orexin's impact on glucose homeostasis in mammalian models. Molecular mechanisms were analyzed and grouped by tissues: central nervous system (CNS), pancreas, liver, skeletal muscle, adipose or vascular tissue, gut, and whole-body systems. Results: Thirty studies were included. Central orexin neurons integrate glycemic inputs via the autonomic nervous system (ANS). Orexin-A stimulates insulin secretion and β-cell proliferation through OX1R/PI3K/Akt/ERK1/2 signaling. It suppresses hepatic gluconeogenesis via PGC-1α downregulation and enhances insulin sensitivity. In adipose tissue, it promotes GLUT4 translocation and adiponectin via PPARγ/C/EBPα, while protecting endothelium from high-glucose damage via SIRT1/NLRP3 inhibition. In the gut, orexin inhibits SGLT-1-mediated glucose absorption through OX1R/OX2R. Systemic orexin deficiency induces insulin resistance, reversible by treatment. Conclusion: The orexinergic pathway serves as a metabolic integrator, linking central glucose sensing with peripheral utilization. Its context-dependent duality, promoting glucose release in hypoglycemia and insulin sensitivity in hyperglycemia, highlights a unique regulatory role. Orexin receptors are promising therapeutic targets for diabetes and metabolic syndrome. Sex-stratified human studies are needed, as preclinical data reveal marked sexual dimorphism in orexin-mediated glucose regulation, with males exhibiting greater metabolic vulnerability to orexin deficiency.
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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 OpenQuestion graph.