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Yang

Yang de Marinis

Associate professor

Yang

Peptide YY (1–36) peptides from phylogenetically ancient fish targeting mammalian neuropeptide Y1 receptors demonstrate potent effects on pancreatic β-cell function, growth and survival

Author

  • Ryan A. Lafferty
  • Neil Tanday
  • Andrew McCloskey
  • Pradeep Bompada
  • Yang De Marinis
  • Peter R. Flatt
  • Nigel Irwin

Summary, in English

Aim: To investigate the antidiabetic efficacy of enzymatically stable Peptide YY (PYY) peptides from phylogenetically ancient fish. Materials and methods: N-terminally stabilized, PYY (1–36) sequences from Amia calva (bowfin), Oncorhynchus mykiss (trout), Petromyzon marinus (sea lamprey) and Scaphirhynchus albus (sturgeon), were synthesized, and both biological actions and antidiabetic therapeutic efficacy were assessed. Results: All fish PYY (1–36) peptides were resistant to dipeptidyl peptidase-4 (DPP-4) degradation and inhibited glucose- and alanine-induced (P < 0.05 to P < 0.001) insulin secretion. In addition, PYY (1–36) peptides imparted significant (P < 0.05 to P < 0.001) β-cell proliferative and anti-apoptotic benefits. Proliferative effects were almost entirely absent in β cells with CRISPR-Cas9-induced knockout of Npyr1. In contrast to human PYY (1–36), the piscine-derived peptides lacked appetite-suppressive actions. Twice-daily administration of sea lamprey PYY (1–36), the superior bioactive peptide, for 21 days significantly (P < 0.05 to P < 0.001) decreased fluid intake, non-fasting glucose and glucagon in streptozotocin (STZ)-induced diabetic mice. In addition, glucose tolerance, insulin sensitivity, pancreatic insulin and glucagon content were significantly improved. Metabolic benefits were linked to positive changes in pancreatic islet morphology as a result of augmented (P < 0.001) proliferation and decreased apoptosis of β cells. Sturgeon PYY (1–36) exerted similar but less impressive effects in STZ mice. Conclusion: These observations reveal, for the first time, that PYY (1–36) peptide sequences from phylogenetically ancient fish replicate the pancreatic β-cell benefits of human PYY (1–36) and have clear potential for the treatment of type 2 diabetes.

Department/s

  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Genomics, Diabetes and Endocrinology

Publishing year

2020

Language

English

Pages

404-416

Publication/Series

Diabetes, Obesity and Metabolism

Volume

22

Issue

3

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Endocrinology and Diabetes

Keywords

  • appetite
  • bowfin
  • degradation
  • insulin secretion
  • lamprey
  • peptide YY (PYY)
  • sturgeon
  • trout
  • β cell

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1462-8902