Hypusinated eIF5A is expressed in the pancreas and spleen of individuals with type 1 and type 2 diabetes

PLoS One. 2020 Mar 24;15(3):e0230627. doi: 10.1371/journal.pone.0230627. eCollection 2020.

Abstract

The 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology*
  • Eukaryotic Translation Initiation Factor 5A
  • Female
  • Humans
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism
  • Lysine / analogs & derivatives*
  • Lysine / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Middle Aged
  • Pancreas / metabolism*
  • Pancreatic Polypeptide-Secreting Cells / cytology
  • Pancreatic Polypeptide-Secreting Cells / metabolism
  • Peptide Initiation Factors / genetics
  • Peptide Initiation Factors / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Spleen / metabolism*
  • Young Adult

Substances

  • Peptide Initiation Factors
  • RNA-Binding Proteins
  • hypusine
  • Lysine