{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:59:12Z","timestamp":1789167552664,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82504394"],"award-info":[{"award-number":["82504394"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U21A20398"],"award-info":[{"award-number":["U21A20398"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Emerging evidence suggests that indole\u20103\u2010propionic acid (IPA), a gut microbiota\u2013derived tryptophan metabolite, confers metabolic benefits in type 2 diabetes (T2D). However, its direct role in preserving pancreatic \u03b2\u2010cell function and the underlying molecular mechanisms remains largely undefined. This study aimed to investigate the role and underlying mechanisms of IPA in preserving \u03b2\u2010cell function and alleviating endoplasmic reticulum (ER) stress under diabetogenic conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>High\u2010fat diet\u2010fed and db\/db mice were treated with IPA via oral gavage. Glucose homeostasis, islet morphology, and insulin secretion were evaluated. In vitro studies in MIN6 cells and isolated islets assessed IPA's effects on ER stress, insulin secretion, and apoptosis. Proteomics, molecular docking, luciferase reporter assays, and gene expression analyses were conducted to identify key molecular targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IPA significantly preserved islet architecture and enhanced insulin secretion. Proteomic analysis revealed downregulation of ER stress pathways and upregulation of SGPP1 upon IPA treatment. SGPP1 was essential for IPA\u2010mediated suppression of ER stress and \u03b2\u2010cell apoptosis through direct interaction with HSPA5. IPA stabilized and activated the transcription factor FOXA1, which in turn transcriptionally upregulated SGPP1 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>IPA protects pancreatic \u03b2\u2010cells by activating the FOXA1\u2013SGPP1\u2013HSPA5 signalling pathway, thereby alleviating ER stress and enhancing \u03b2\u2010cell survival.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70471","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T09:00:00Z","timestamp":1768986000000},"page":"2884-2897","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Oral indole\u20103\u2010propionic acid preserves \u03b2\u2010cell function and improves glucose homeostasis in diabetic mice via\n                    <scp>FOXA1<\/scp>\n                    \u2013\n                    <scp>SGPP1<\/scp>\n                    \u2013\n                    <scp>HSPA5<\/scp>\n                    signalling"],"prefix":"10.1111","volume":"28","author":[{"given":"Xin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education Harbin Medical University  Harbin P. R. China"},{"name":"Department of Endocrinology The Second Affiliated Hospital of Harbin Medical University  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixiao","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education Harbin Medical University  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hepatopancreatobiliary Surgery Harbin Medical University Cancer Hospital  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education Harbin Medical University  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyao","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education Harbin Medical University  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology The Second Affiliated Hospital of Harbin Medical University  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education Harbin Medical University  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education Harbin Medical University  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjian","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education Harbin Medical University  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9416-7044","authenticated-orcid":false,"given":"Changhao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education Harbin Medical University  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2294-630X","authenticated-orcid":false,"given":"Huanyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education Harbin Medical University  Harbin P. R. China"},{"name":"Department of Cardiology, The Key Laboratory of Myocardial Ischemia The Second Affiliated Hospital of Harbin Medical University, Chinese Ministry of Education  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01301-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/AITC202406180"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-024-00563-5"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2024.108724"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01842-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01951-9"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3712-7"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-306928"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods10071590"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2392864"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.09.032"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.02.019"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-024-01750-y"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13283"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep46337"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107207"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.001"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.02.022"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.123.322381"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2024.03.011"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04884-x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-024-01755-7"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.321253"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102451"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20040857"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2008.07.014"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2017.03.005"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2018.11.014"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2040-1124.2010.00021.x"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082813"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.1.102"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05470-4"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2018.05.003"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200203123"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2010.104"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2015.4162"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2004.10.010"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3800"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2009-0513"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-006-6095-6"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1801745115"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adi3332"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.70471","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/full-xml\/10.1111\/dom.70471","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.70471","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T04:25:13Z","timestamp":1773807913000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.70471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/dom.70471"],"URL":"https:\/\/doi.org\/10.1111\/dom.70471","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.70471\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70471\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70471\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70471\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70471\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70471\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70471\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70471\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70471\/v2\/decision1","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"assertion":[{"value":"2025-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}