{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sims EK"],"funding":["BLRD VA","Juvenile Diabetes Research Foundation United States of America","NCATS NIH HHS","Indiana University","NIDDK NIH HHS","Doris Duke Charitable Foundation","NIAID NIH HHS","National Institutes of Health","JDRF","John Templeton Foundation"],"pagination":["101261"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10694631"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["4(11)"],"pubmed_abstract":["In preclinical models, α-difluoromethylornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, delays the onset of type 1 diabetes (T1D) by reducing β cell stress. However, the mechanism of DFMO action and its human tolerability remain unclear. In this study, we show that mice with β cell ODC deletion are protected against toxin-induced diabetes, suggesting a cell-autonomous role of ODC during β cell stress. In a randomized controlled trial (ClinicalTrials.gov: NCT02384889) involving 41 recent-onset T1D subjects (3:1 drug:placebo) over a 3-month treatment period with a 3-month follow-up, DFMO (125-1,000 mg/m<sup>2</sup>) is shown to meet its primary outcome of safety and tolerability. DFMO dose-dependently reduces urinary putrescine levels and, at higher doses, preserves C-peptide area under the curve without apparent immunomodulation. Transcriptomics and proteomics of DFMO-treated human islets exposed to cytokine stress reveal alterations in mRNA translation, nascent protein transport, and protein secretion. These findings suggest that DFMO may preserve β cell function in T1D through islet cell-autonomous effects."],"journal":["Cell reports. Medicine"],"pubmed_title":["Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes."],"pmcid":["PMC10694631"],"funding_grant_id":["R01 DK121987","U01 DK127786","62288","T32 AI153020","UL1 TR002529","P30 DK097512","I01 BX001733","2021258","3-SRA-2015-7-M-R","R01 DK127236","P30 DK020595","R01 DK060581","R01 DK133881","R01 DK121929","R01 DK127308","R01 DK124906"],"pubmed_authors":["Blanchfield L","Mirmira RG","Mastrandrea LD","Nakayasu ES","Woerner SE","Sims EK","Hammoud B","Hull A","Webb-Robertson BJ","Kulkarni A","Long SA","Cabrera S","Sarkar S","Ouyang F","Evans-Molina C","Perkins SM","Enriquez JR","Gerner EW","Tersey SA","Mastracci TL","DiMeglio LA"],"additional_accession":[]},"is_claimable":false,"name":"Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes.","description":"In preclinical models, α-difluoromethylornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, delays the onset of type 1 diabetes (T1D) by reducing β cell stress. However, the mechanism of DFMO action and its human tolerability remain unclear. In this study, we show that mice with β cell ODC deletion are protected against toxin-induced diabetes, suggesting a cell-autonomous role of ODC during β cell stress. In a randomized controlled trial (ClinicalTrials.gov: NCT02384889) involving 41 recent-onset T1D subjects (3:1 drug:placebo) over a 3-month treatment period with a 3-month follow-up, DFMO (125-1,000 mg/m<sup>2</sup>) is shown to meet its primary outcome of safety and tolerability. DFMO dose-dependently reduces urinary putrescine levels and, at higher doses, preserves C-peptide area under the curve without apparent immunomodulation. Transcriptomics and proteomics of DFMO-treated human islets exposed to cytokine stress reveal alterations in mRNA translation, nascent protein transport, and protein secretion. These findings suggest that DFMO may preserve β cell function in T1D through islet cell-autonomous effects.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Nov","modification":"2026-06-23T03:20:59.485Z","creation":"2025-02-19T04:25:28.226Z"},"accession":"S-EPMC10694631","cross_references":{"pubmed":["37918404"],"doi":["10.1016/j.xcrm.2023.101261"]}}