[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-407046-105":59,"doc-detail-407046-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","xenin-derived-peptides-multifaceted-regulators-and-therapeutic-innovations-in-metabolic-diseases","Xenin-Derived Peptides: Multifaceted Regulators and Therapeutic Innovations in Metabolic Diseases","","Xenin, a 25-amino-acid peptide hormone secreted primarily by intestinal K cells, is evolutionarily conserved with related neuropeptides and signals through NTSR1 to regulate appetite and glucose homeostasis in coordinated pathways involving incretin hormones. Preclinical work indicates dual benefits: appetite suppression and enhanced pancreatic β-cell survival. A limited pilot in humans suggests delayed gastric emptying and reduced postprandial glucose rises, pending independent validation. Engineered xenin analogues improve metabolic stability, extend half-life, and in models enhance insulin secretion and incretin responsiveness, including synergistic multi-agonist designs. Translational challenges include receptor cross-talk mechanisms and species-specific gastrointestinal responses, requiring rigorous pharmacokinetic profiling and phased trials.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/xenin-derived-peptides-multifaceted-regulators-and-therapeutic-innovations-in-metabolic-diseases/407046/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/xenin-derived-peptides-multifaceted-regulators-and-therapeutic-innovations-in-metabolic-diseases/407046.png","ImageObject",300,407,{"name":92,"@type":93},"anakgang17","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How does xenin regulate appetite and glucose homeostasis?","Question",{"text":113,"@type":114},"Xenin interacts with NTSR1 to influence hypothalamic signaling and appetite regulation. It also modulates glucose homeostasis through synergistic interactions within incretin hormone pathways.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What limits native xenin as a therapeutic candidate?",{"text":118,"@type":114},"Native xenin is constrained by rapid proteolytic degradation and limited bioavailability, leading to a short effective half-life (about 5–10 minutes) and quick loss of activity.",{"name":120,"@type":111,"acceptedAnswer":121},"What strategies improve xenin’s pharmacokinetics and therapeutic potential?",{"text":122,"@type":114},"Peptide engineering such as C-terminal truncation, site-directed amino acid substitution, and lipidation generates analogues with prolonged metabolic activity and longer plasma half-life. Hybrid and multi-agonist designs combining xenin with other gastrointestinal hormones aim to enhance insulin secretion and reduce energy intake in preclinical studies.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},407046,1790785214,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},962090883568,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Drug Design, Development and Therapy  \n Open Access Full Text Article  \nREVIEW  \nXenin-Derived Peptides: Multifaceted Regulators and Therapeutic Innovations in Metabolic Diseases  \nBinbin Gong 1 , 2 , *, Xiyu Liu 1 , 2 , *, Guoqiang Hu 1 , Tongtong Li2 , Fei Chen2 , Xueqing Sun2 , Lidan Sun 1 , 2 , Yinghe Xu 1  \n1Taizhou Hospital, Zhejiang University, Taizhou, 317000, People’s Republic of China; 2College of Medicine, Jiaxing University, Jiaxing, 314001, People’s Republic of China  \n*These authors contributed equally to this work  \nCorrespondence: Lidan Sun; Yinghe Xu, Taizhou Hospital, Zhejiang University, Taizhou, 317000, People’s Republic of China, Tel +86-18358328736, Fax +86-573-83643848, Email [slidan89@zjxu.edu.cn](slidan89@zjxu.edu.cn); [xuyh@enzemed.com](xuyh@enzemed.com)  \n\n| Abstract: Xenin, a 25-amino acid peptide hormone predominantly secreted by intestinal K cells, demonstrates evolutionary conservation with neuropeptides such as xenopsin and neurotensin. Functionally, it engages neurotensin receptor 1 (NTSR1) to regulate appetite via hypothalamic signaling pathways and modulates glucose homeostasis through synergistic interactions withincretin hormones. Preclinical studies highlight its dual role in suppressing appetite and enhancing pancreatic β-cell survival, while a single pilot human study suggests xenin-25 may delay gastric emptying and attenuate postprandial glucose excursions; however, these data await independent confirmation. Native xenin, however, is constrained by rapid proteolytic degradation and limited bioavailability. Advances in peptide engineering, including C-terminal truncation, site-directed amino acid substitution, and lipidation, have generated analogues that exhibit prolonged metabolic activity in rodent models, with plasma half-life extended from minutes to hours. In murine models of metabolic dysfunction, these derivatives enhance insulin secretion, improve glycaemic profiles and restore incretin responsiveness. Furthermore, multi-agonist peptides combining xenin with other gastrointestinal hormones show synergistic potential in preclinical studies, concurrently augmenting insulin secretion and reducing energy intake, though their clinical relevance remains to be validated in human trials. Despite promising preclinical outcomes, challenges persist in translating xenin-based therapies to clinical practice, including incomplete mechanistic insights into receptor cross-talk and species-specific variations in gastrointestinal responses. This review uniquely integrates the preclinical landscape of xenin biology, peptide-engineering principles, and emerging multi-agonist design, identifying knowledge gaps critical for future translation. We conclude that xenin-based therapeutics area promising yet early-stage strategy whose efficacy and safety in human metabolic diseases remain to be established through rigorous pharmacokinetic profiling and phased clinical trials.\u003Cbr>keywords: Xenin, type 2 diabetes, obesity, physiological function, structural modification |\n| --- |\n| Introduction\u003Cbr>Xenin is a 25-amino acid peptide hormone primarily secreted by enteroendocrine K cells in the gastrointestinal tract, particularly in the gastric and duodenal mucosa.1,2 Its secretion is closely associated with fasting and postprandial states, with plasma levels peaking during the migratory motor complex Phase III in humans.3 The species, in proteins of which the xenin motifs were identified with a highest degree of homology to human xenin. Motifs with 40% homology to human xenin are already present in prokaryotes. Homology reaches 84–96% in single-cell algae and plants, becoming complete since bony fishes (see Table 1) .4\u003Cbr>Xenin exhibits structural homology with neurotensin and amphibian xenopsin, sharing evolutionary conservation across vertebrates, and is derived from the proteolytic cleavage of its precursor, proxenin, which is homologous to cytoplasmic coatomer protein subunit α .4 Functionally, xenin modul","cbCairmhEGRbz5YO","https://ap.wps.com/l/cbCairmhEGRbz5YO","pdf",6043066,17,"English","# Abstract\n# Introduction","[{\"question\":\"How does xenin regulate appetite and glucose homeostasis?\",\"answer\":\"Xenin interacts with NTSR1 to influence hypothalamic signaling and appetite regulation. It also modulates glucose homeostasis through synergistic interactions within incretin hormone pathways.\"},{\"question\":\"What limits native xenin as a therapeutic candidate?\",\"answer\":\"Native xenin is constrained by rapid proteolytic degradation and limited bioavailability, leading to a short effective half-life (about 5–10 minutes) and quick loss of activity.\"},{\"question\":\"What strategies improve xenin’s pharmacokinetics and therapeutic potential?\",\"answer\":\"Peptide engineering such as C-terminal truncation, site-directed amino acid substitution, and lipidation generates analogues with prolonged metabolic activity and longer plasma half-life. Hybrid and multi-agonist designs combining xenin with other gastrointestinal hormones aim to enhance insulin secretion and reduce energy intake in preclinical studies.\"}]","Xenin-Derived Peptides: Multifaceted Regulators and Therapeutic Innovations in Metabolic Diseases | PDF",1790569817,43]