Polyamine biosynthesis is critical for growth and differentiation of the pancreas

Teresa L. Mastracci, Morgan A. Robertson, Raghu Mirmira, Ryan M. Anderson

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The pancreas, in most studied vertebrates, is a compound organ with both exocrine and endocrine functions. The exocrine compartment makes and secretes digestive enzymes, while the endocrine compartment, organized into islets of Langerhans, produces hormones that regulate blood glucose. High concentrations of polyamines, which are aliphatic amines, are reported in exocrine and endocrine cells, with insulin-producing β cells showing the highest concentrations. We utilized zebrafish as a model organism, together with pharmacological inhibition or genetic manipulation, to determine how polyamine biosynthesis functions in pancreatic organogenesis. We identified that inhibition of polyamine biosynthesis reduces exocrine pancreas and β cell mass, and that these reductions are at the level of differentiation. Moreover, we demonstrate that inhibition of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, phenocopies inhibition or knockdown of the enzyme deoxyhypusine synthase (DHS). These data identify that the pancreatic requirement for polyamine biosynthesis is largely mediated through a requirement for spermidine for the downstream posttranslational modification of eIF5A by its enzymatic activator DHS, which in turn impacts mRNA translation. Altogether, we have uncovered a role for polyamine biosynthesis in pancreatic organogenesis and identified that it may be possible to exploit polyamine biosynthesis to manipulate pancreatic cell differentiation.

Original languageEnglish (US)
Article number13269
JournalScientific Reports
Volume5
DOIs
StatePublished - Aug 24 2015

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Polyamines
Pancreas
Growth
Organogenesis
Enzymes
Exocrine Pancreas
Ornithine Decarboxylase
Spermidine
Endocrine Cells
Protein Biosynthesis
Zebrafish
Post Translational Protein Processing
Islets of Langerhans
Amines
Blood Glucose
Vertebrates
Cell Differentiation
Hormones
Pharmacology
Insulin

ASJC Scopus subject areas

  • General

Cite this

Polyamine biosynthesis is critical for growth and differentiation of the pancreas. / Mastracci, Teresa L.; Robertson, Morgan A.; Mirmira, Raghu; Anderson, Ryan M.

In: Scientific Reports, Vol. 5, 13269, 24.08.2015.

Research output: Contribution to journalArticle

Mastracci, Teresa L. ; Robertson, Morgan A. ; Mirmira, Raghu ; Anderson, Ryan M. / Polyamine biosynthesis is critical for growth and differentiation of the pancreas. In: Scientific Reports. 2015 ; Vol. 5.
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