{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Herlea-Pana O"],"funding":["NIDDK NIH HHS","National Institutes of Health"],"pagination":["749879"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8524045"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12"],"pubmed_abstract":["β-cell ER stress plays an important role in β-cell dysfunction and death during the pathogenesis of diabetes. Proinsulin misfolding is regarded as one of the primary initiating factors of ER stress and unfolded protein response (UPR) activation in β-cells. Here, we found that the ER stress sensor inositol-requiring enzyme 1α (IRE1α) was activated in the Akita mice, a mouse model of mutant insulin gene-induced diabetes of youth (MIDY), a monogenic diabetes. Normalization of IRE1α RNase hyperactivity by pharmacological inhibitors significantly ameliorated the hyperglycemic conditions and increased serum insulin levels in Akita mice. These benefits were accompanied by a concomitant protection of functional β-cell mass, as shown by the suppression of β-cell apoptosis, increase in mature insuli"],"journal":["Frontiers in endocrinology"],"pubmed_title":["Pharmacological Inhibition of Inositol-Requiring Enzyme 1α RNase Activity Protects Pancreatic Beta Cell and Improves Diabetic Condition in Insulin Mutation-Induced Diabetes."],"pmcid":["PMC8524045"],"funding_grant_id":["DK108887, DK116017, GM103636","R01 DK116017","R56 DK108887"],"pubmed_authors":["Herlea-Pana O","Undi RB","Wang W","Lim HY","Eeda V"],"additional_accession":[]},"is_claimable":false,"name":"Pharmacological Inhibition of Inositol-Requiring Enzyme 1α RNase Activity Protects Pancreatic Beta Cell and Improves Diabetic Condition in Insulin Mutation-Induced Diabetes.","description":"β-cell ER stress plays an important role in β-cell dysfunction and death during the pathogenesis of diabetes. Proinsulin misfolding is regarded as one of the primary initiating factors of ER stress and unfolded protein response (UPR) activation in β-cells. Here, we found that the ER stress sensor inositol-requiring enzyme 1α (IRE1α) was activated in the Akita mice, a mouse model of mutant insulin gene-induced diabetes of youth (MIDY), a monogenic diabetes. Normalization of IRE1α RNase hyperactivity by pharmacological inhibitors significantly ameliorated the hyperglycemic conditions and increased serum insulin levels in Akita mice. These benefits were accompanied by a concomitant protection of functional β-cell mass, as shown by the suppression of β-cell apoptosis, increase in mature insuli","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021","modification":"2025-04-04T10:55:52.496Z","creation":"2025-04-04T10:55:52.496Z"},"accession":"S-EPMC8524045","cross_references":{"pubmed":["34675883"],"doi":["10.3389/fendo.2021.749879"]}}