Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes

• Published in: Cell reports. Medicine Vol. 4; no. 11; p. 101261
• Main Authors: Sims, Emily K., Kulkarni, Abhishek, Hull, Audrey, Woerner, Stephanie E., Cabrera, Susanne, Mastrandrea, Lucy D., Hammoud, Batoul, Sarkar, Soumyadeep, Nakayasu, Ernesto S., Mastracci, Teresa L., Perkins, Susan M., Ouyang, Fangqian, Webb-Robertson, Bobbie-Jo, Enriquez, Jacob R., Tersey, Sarah A., Evans-Molina, Carmella, Long, S. Alice, Blanchfield, Lori, Gerner, Eugene W., Mirmira, Raghavendra G., DiMeglio, Linda A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.11.2023; Cell Press; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Advanced Basic Science; Animals; Diabetes Mellitus, Type 1 - drug therapy; disease modification; Eflornithine - pharmacology; Eflornithine - therapeutic use; Humans; islet; Mice; ornithine decarboxylase; Ornithine Decarboxylase - genetics; Ornithine Decarboxylase - metabolism; Ornithine Decarboxylase Inhibitors - pharmacology; polyamines; prevention; Putrescine - metabolism; trial; type 1 diabetes; α-difluoromethylornithine; β cell; β cell stress; type 1 diabetes; α-difluoromethylornithine; β cell stress; β cell; ornithine decarboxylase; islet; polyamines; prevention; trial; disease modification

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...