ArticleThe Journal of biological chemistry2010
Xenin-25 potentiates glucose-dependent insulinotropic polypeptide action via a novel cholinergic relay mechanism.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 71 citations in OpenAlex.
- Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without type 2 diabetes.American journal of physiology. Gastrointestinal and liver physiology · 2014Trial
- Xenin-25 amplifies GIP-mediated insulin secretion in humans with normal and impaired glucose tolerance but not type 2 diabetes.Diabetes · 2012Trial
- Xenin-25 improves indomethacin-induced acute gastric injury in rats.Pflugers Archiv : European journal of physiology · 2026Article
- The evaluation of Xenin-25 levels in intrahepatic cholestasis of pregnancy and comparison with healthy pregnant women.BMC pregnancy and childbirth · 2026Article
- Xenin-Derived Peptides: Multifaceted Regulators and Therapeutic Innovations in Metabolic Diseases.Drug design, development and therapy · 2025Review
- Review of Novel Potential Insulin Resistance Biomarkers in PCOS Patients-The Debate Is Still Open.International journal of environmental research and public health · 2022Review
- A novel neurotensin/xenin fusion peptide enhances β-cell function and exhibits antidiabetic efficacy in high-fat fed mice.Bioscience reports · 2021Article
- Nutrient-Induced Cellular Mechanisms of Gut Hormone Secretion.Nutrients · 2021Review
- Xenin and Related Peptides: Potential Therapeutic Role in Diabetes and Related Metabolic Disorders.Clinical medicine insights. Endocrinology and diabetes · 2021Review
- Neurotensin and Xenin Show Positive Correlations With Perceived Stress, Anxiety, Depressiveness and Eating Disorder Symptoms in Female Obese Patients.Frontiers in behavioral neuroscience · 2021Article
- Multiagonist Unimolecular Peptides for Obesity and Type 2 Diabetes: Current Advances and Future Directions.Clinical medicine insights. Endocrinology and diabetes · 2020Review
- Nonclassical Islet Peptides: Pancreatic and Extrapancreatic Actions.Clinical medicine insights. Endocrinology and diabetes · 2019Review
- Article
- Xenin is a novel anorexigen in goldfish (Carassius auratus).PloS one · 2018Article
- Xenin Augments Duodenal Anion Secretion via Activation of Afferent Neural Pathways.The Journal of pharmacology and experimental therapeutics · 2017Article
- An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice.Diabetologia · 2017Article
- Dietary steamed wheat bran increases postprandial fat oxidation in association with a reduced blood glucose-dependent insulinotropic polypeptide response in mice.Food & nutrition research · 2017Article
- c-Fos induction by gut hormones and extracellular ATP in osteoblastic-like cell lines.Purinergic signalling · 2016Article
- Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery.Peptides · 2016Article
- Inter-organ communication and regulation of beta cell function.Diabetologia · 2016Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
The intestinal peptides GLP-1 and GIP potentiate glucose-mediated insulin release. Agents that increase GLP-1 action are effective therapies in type 2 diabetes mellitus (T2DM). However, GIP action is blunted in T2DM, and GIP-based therapies have not been developed. Thus, it is important to increase our understanding of the mechanisms of GIP action. We developed mice lacking GIP-producing K cells. Like humans with T2DM, "GIP/DT" animals exhibited a normal insulin secretory response to exogenous GLP-1 but a blunted response to GIP. Pharmacologic doses of xenin-25, another peptide produced by K cells, restored the GIP-mediated insulin secretory response and reduced hyperglycemia in GIP/DT mice. Xenin-25 alone had no effect. Studies with islets, insulin-producing cell lines, and perfused pancreata indicated xenin-25 does not enhance GIP-mediated insulin release by acting directly on the beta-cell. The in vivo effects of xenin-25 to potentiate insulin release were inhibited by atropine sulfate and atropine methyl bromide but not by hexamethonium. Consistent with this, carbachol potentiated GIP-mediated insulin release from in situ perfused pancreata of GIP/DT mice. In vivo, xenin-25 did not activate c-fos expression in the hind brain or paraventricular nucleus of the hypothalamus indicating that central nervous system activation is not required. These data suggest that xenin-25 potentiates GIP-mediated insulin release by activating non-ganglionic cholinergic neurons that innervate the islets, presumably part of an enteric-neuronal-pancreatic pathway. Xenin-25, or molecules that increase acetylcholine receptor signaling in beta-cells, may represent a novel approach to overcome GIP resistance and therefore treat humans with T2DM.
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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.