{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin HH"],"funding":["National Health Research Institutes (NHRI)"],"pagination":["10537"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11615295"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["SPINT1, a membrane-anchored serine protease inhibitor, regulates cascades of pericellular proteolysis while its tissue-specific functions remain incompletely characterized. In this study, we generate Spint1-lacZ knock-in mice and observe Spint1 expression in embryonic pancreatic epithelium. Pancreas-specific Spint1 disruption significantly diminishes islet size and mass, causing glucose intolerance and downregulation of MAFA and insulin. Mechanistically, the serine protease HEPSIN interacts with SPINT1 in β cells, and Hepsin silencing counteracts the downregulation of Mafa and Ins1 caused by Spint1 depletion. Furthermore, we demonstrate a potential interaction between HEPSIN and GLP1R in β cells. Spint1 silencing or Hepsin overexpression reduces GLP1R-related cyclic AMP levels and Mafa exp"],"journal":["Nature communications"],"pubmed_title":["Spint1 disruption in mouse pancreas leads to glucose intolerance and impaired insulin production involving HEPSIN/MAFA."],"pmcid":["PMC11615295"],"funding_grant_id":["EX109-10725BI"],"pubmed_authors":["Cheng MS","Lin HH","Huang SY","Lin HY","Huang HP","Chen TY","Chang YC","Ko CJ","Kan KW","Chen PH","Huang TC","Lee MS","Yu IS","Lin SW","Chang TJ"],"additional_accession":[]},"is_claimable":false,"name":"Spint1 disruption in mouse pancreas leads to glucose intolerance and impaired insulin production involving HEPSIN/MAFA.","description":"SPINT1, a membrane-anchored serine protease inhibitor, regulates cascades of pericellular proteolysis while its tissue-specific functions remain incompletely characterized. In this study, we generate Spint1-lacZ knock-in mice and observe Spint1 expression in embryonic pancreatic epithelium. Pancreas-specific Spint1 disruption significantly diminishes islet size and mass, causing glucose intolerance and downregulation of MAFA and insulin. Mechanistically, the serine protease HEPSIN interacts with SPINT1 in β cells, and Hepsin silencing counteracts the downregulation of Mafa and Ins1 caused by Spint1 depletion. Furthermore, we demonstrate a potential interaction between HEPSIN and GLP1R in β cells. Spint1 silencing or Hepsin overexpression reduces GLP1R-related cyclic AMP levels and Mafa exp","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2025-04-18T12:52:34.712Z","creation":"2025-04-06T22:14:27.335Z"},"accession":"S-EPMC11615295","cross_references":{"pubmed":["39627229"],"doi":["10.1038/s41467-024-54927-2"]}}