{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:03Z","timestamp":1784557023719,"version":"3.55.0"},"reference-count":48,"publisher":"Bioscientifica","issue":"11","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,5]]},"abstract":"<jats:p>Glucose-like peptide-1 (GLP-1) is a vital hormone in the intestines that regulates glucose metabolism. Although pancreatic-derived factor (PANDER) overexpression is known to suppress GLP-1, the underlying mechanisms are unclear. Our study aims to uncover how PANDER influences GLP-1 synthesis and secretion. We established a PANDER overexpression model in STC-1 intestinal cells, confirming its inhibitory effect on GLP-1 secretion. This effect was reversed in PANDER-knockout cells. Additionally, a negative correlation between PANDER and GLP-1 was observed in patients with a history of gestational diabetes. Subsequently, through whole transcriptome gene sequencing in PANDER-overexpressed STC-1 cells, we discovered that the activation of IL-6 and its related STAT3 signaling pathway was significantly inhibited, and this finding was validated by Western blotting and quantitative reverse transcription PCR. Finally, rescue experiments confirmed that the IL-6-related STAT3\/Akt\/GSK3\u03b2\/\u03b2-catenin signaling pathway mediates the negative regulatory effect of PANDER on GLP-1. Taken together, our data identify IL-6 as a bridge connecting PANDER and GLP-1 in the STC-1 cells, demonstrating potential therapeutic targets for diabetes treatment by targeting the PANDER\u2013IL-6\u2013GLP-1 axis.<\/jats:p>","DOI":"10.1530\/ec-23-0548","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T11:46:52Z","timestamp":1725536812000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":4,"title":["The role of PANDER and its interplay with IL-6 in the regulation of GLP-1 secretion"],"prefix":"10.1530","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3151-4568","authenticated-orcid":true,"given":"Zeting","family":"Li","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangmeng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghua","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufang","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changliu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3782-9210","authenticated-orcid":true,"given":"Yanbing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haipeng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4402-7032","authenticated-orcid":true,"given":"Xiaopei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Nature","first-page":"368","article-title":"Exon duplication and divergence in the human preproglucagon gene","volume":"304","author":"Bell","year":"1983","unstructured":"Bell GISanchez-Pescador RLaybourn PJ & Najarian RC. 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