Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Lafferty, Ryan A. ; Tanday, Neil ; McCloskey, Andrew ; Bompada, Pradeep LU ; De Marinis, Yang LU ; Flatt, Peter R. and Irwin, Nigel (2020) In Diabetes, Obesity and Metabolism 22(3). p.404-416
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
appetite, bowfin, degradation, insulin secretion, lamprey, peptide YY (PYY), sturgeon, trout, β cell
in
Diabetes, Obesity and Metabolism
volume
22
issue
3
pages
13 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85076213038
  • pmid:31692207
ISSN
1462-8902
DOI
10.1111/dom.13908
language
English
LU publication?
yes
id
f62e15db-b03a-45c5-9a04-b22e1a49895a
date added to LUP
2020-12-28 12:09:58
date last changed
2024-03-20 22:08:04
@article{f62e15db-b03a-45c5-9a04-b22e1a49895a,
  abstract     = {{<p>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 &lt; 0.05 to P &lt; 0.001) insulin secretion. In addition, PYY (1–36) peptides imparted significant (P &lt; 0.05 to P &lt; 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 &lt; 0.05 to P &lt; 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 &lt; 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.</p>}},
  author       = {{Lafferty, Ryan A. and Tanday, Neil and McCloskey, Andrew and Bompada, Pradeep and De Marinis, Yang and Flatt, Peter R. and Irwin, Nigel}},
  issn         = {{1462-8902}},
  keywords     = {{appetite; bowfin; degradation; insulin secretion; lamprey; peptide YY (PYY); sturgeon; trout; β cell}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{404--416}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Diabetes, Obesity and Metabolism}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1111/dom.13908}},
  doi          = {{10.1111/dom.13908}},
  volume       = {{22}},
  year         = {{2020}},
}