ArticleScientific reports2015
Polyamine biosynthesis is critical for growth and differentiation of the pancreas.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Difluoromethylornithine modulates mutant K-RAS signaling pathways in pancreatic cancer cells.Amino acids · 2026Article
- Using animal models to decipher the role of polyamines in the pancreas and β Cell.Amino acids · 2026Review
- Single-Cell Multiome Impact of Prenatal Heavy Metal Exposure on Early Airway Development.American journal of respiratory cell and molecular biology · 2026Article
- Hypusinated and unhypusinated isoforms of the translation factor eIF5A exert distinct effects in models of pancreas development and function.The Journal of biological chemistry · 2025Article
- The Associations of Dietary Polyamines with Incident Type 2 Diabetes Mellitus: A Large Prospective Cohort Study.Nutrients · 2025Article
- Spermidine mediates acetylhypusination of RIPK1 to suppress diabetes onset and progression.Nature cell biology · 2024Article
- Deoxyhypusine synthase deficiency syndrome zebrafish model: aberrant morphology, epileptiform activity, and reduced arborization of inhibitory interneurons.Molecular brain · 2024Article
- A Translational Regulatory Mechanism Mediated by Hypusinated Eukaryotic Initiation Factor 5A Facilitates β-Cell Identity and Function.Diabetes · 2024Article
- Comparative transcriptomic analysis reveals the underlying molecular mechanism in high-fat diet-induced islet dysfunction.Bioscience reports · 2023Article
- Deoxyhypusine synthase mutations alter the post-translational modification of eukaryotic initiation factor 5A resulting in impaired human and mouse neural homeostasis.HGG advances · 2023Article
- New K50R mutant mouse models reveal impaired hypusination of eif5a2 with alterations in cell metabolite landscape.Biology open · 2023Article
- Role of Polyamines and Hypusine in β Cells and Diabetes Pathogenesis.Metabolites · 2022Review
- A Pilot Single Cell Analysis of the Zebrafish Embryo Cellular Responses to UropathogenicPathogens & immunity · 2022Article
- A Blood-based Polyamine Signature Associated With MEN1 Duodenopancreatic Neuroendocrine Tumor Progression.The Journal of clinical endocrinology and metabolism · 2021Article
- Deoxyhypusine synthase promotes a pro-inflammatory macrophage phenotype.Cell metabolism · 2021Article
- Deoxyhypusine synthase, an essential enzyme for hypusine biosynthesis, is required for proper exocrine pancreas development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Impaired eIF5A function causes a Mendelian disorder that is partially rescued in model systems by spermidine.Nature communications · 2021Article
- The Gut Microbial Endocrine Organ in Type 2 Diabetes.Endocrinology · 2021Review
- A 12-lipoxygenase-Gpr31 signaling axis is required for pancreatic organogenesis in the zebrafish.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
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4 authors at 2 institutions in 1 country.
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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.
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