Mastracci, Teresa L.Colvin, Stephanie C.Padgett, Leah R.Mirmira, Raghavendra G.2020-06-232020-06-232020Mastracci, T. L., Colvin, S. C., Padgett, L. R., & Mirmira, R. G. (2020). Hypusinated eIF5A is expressed in the pancreas and spleen of individuals with type 1 and type 2 diabetes. PloS one, 15(3), e0230627. https://doi.org/10.1371/journal.pone.0230627https://hdl.handle.net/1805/23063The gene encoding eukaryotic initiation factor 5A (EIF5A) is found in diabetes-susceptibility loci in mouse and human. eIF5A is the only protein known to contain hypusine (hydroxyputrescine lysine), a polyamine-derived amino acid formed post-translationally in a reaction catalyzed by deoxyhypusine synthase (DHPS). Previous studies showed pharmacologic blockade of DHPS in type 1 diabetic NOD mice and type 2 diabetic db/db mice improved glucose tolerance and preserved beta cell mass, which suggests that hypusinated eIF5A (eIF5AHyp) may play a role in diabetes pathogenesis by direct action on the beta cells and/or altering the adaptive or innate immune responses. To translate these findings to human, we examined tissue from individuals with and without type 1 and type 2 diabetes to determine the expression of eIF5AHyp. We detected eIF5AHyp in beta cells, exocrine cells and immune cells; however, there was also unexpected enrichment of eIF5AHyp in pancreatic polypeptide-expressing PP cells. Interestingly, the presence of eIF5AHyp co-expressing PP cells was not enhanced with disease. These data identify new aspects of eIF5A biology and highlight the need to examine human tissue to understand disease.en-USAttribution 4.0 InternationalEukaryotic initiation factor 5ADiabetes-susceptibilityHypusineDeoxyhypusine synthaseBeta cellsExocrine cellsImmune cellsPP cellsHuman tissue examinationArticle