{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jeffrey KD"],"funding":["NIDDK NIH HHS","NCRR NIH HHS"],"pagination":["8452-7"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2448857"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["105(24)"],"pubmed_abstract":["Obesity is a principal risk factor for type 2 diabetes, and elevated fatty acids reduce beta-cell function and survival. An unbiased proteomic screen was used to identify targets of palmitate in beta-cell death. The most significantly altered protein in both human islets and MIN6 beta-cells treated with palmitate was carboxypeptidase E (CPE). Palmitate reduced CPE protein levels within 2 h, preceding endoplasmic reticulum (ER) stress and cell death, by a mechanism involving CPE translocation to Golgi and lysosomal degradation. Palmitate metabolism and Ca(2+) flux were also required for CPE proteolysis and beta-cell death. Chronic palmitate exposure increased the ratio of proinsulin to insulin. CPE null islets had increased apoptosis in vivo and in vitro. Reducing CPE by approximately 30% u"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Carboxypeptidase E mediates palmitate-induced beta-cell ER stress and apoptosis."],"pmcid":["PMC2448857"],"funding_grant_id":["P41RR00954","R37 DK031842","DK31842","F31 DK079346","R01 DK031842","P30 DK052574","P41 RR000954"],"pubmed_authors":["Li H","Jeffrey KD","Townsend RR","Polonsky KS","Kalynyak TB","Hu X","Luciani DS","Johnson JD","Lin Y","Alejandro EU"],"additional_accession":[]},"is_claimable":false,"name":"Carboxypeptidase E mediates palmitate-induced beta-cell ER stress and apoptosis.","description":"Obesity is a principal risk factor for type 2 diabetes, and elevated fatty acids reduce beta-cell function and survival. An unbiased proteomic screen was used to identify targets of palmitate in beta-cell death. The most significantly altered protein in both human islets and MIN6 beta-cells treated with palmitate was carboxypeptidase E (CPE). Palmitate reduced CPE protein levels within 2 h, preceding endoplasmic reticulum (ER) stress and cell death, by a mechanism involving CPE translocation to Golgi and lysosomal degradation. Palmitate metabolism and Ca(2+) flux were also required for CPE proteolysis and beta-cell death. Chronic palmitate exposure increased the ratio of proinsulin to insulin. CPE null islets had increased apoptosis in vivo and in vitro. Reducing CPE by approximately 30% u","dates":{"release":"2008-01-01T00:00:00Z","publication":"2008 Jun","modification":"2025-04-04T18:33:56.984Z","creation":"2019-03-27T00:15:46Z"},"accession":"S-EPMC2448857","cross_references":{"pubmed":["18550819"],"doi":["10.1073/pnas.0711232105"]}}