Peptide YY (1-36) peptides from phylogenetically ancient fish targeting mammalian neuropeptide Y1 receptors demonstrate potent effects on pancreatic ß-cell function, growth and survival.
Diabetes Obes Metab
; 22(3): 404-416, 2020 03.
Article
en En
| MEDLINE
| ID: mdl-31692207
ABSTRACT
AIM:
To investigate the antidiabetic efficacy of enzymatically stable Peptide YY (PYY) peptides from phylogenetically ancient fish. MATERIALS ANDMETHODS:
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) ß-cell proliferative and anti-apoptotic benefits. Proliferative effects were almost entirely absent in ß 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 ß 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 ß-cell benefits of human PYY (1-36) and have clear potential for the treatment of type 2 diabetes.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neuropéptidos
/
Diabetes Mellitus Experimental
/
Diabetes Mellitus Tipo 2
Límite:
Animals
Idioma:
En
Revista:
Diabetes Obes Metab
Asunto de la revista:
ENDOCRINOLOGIA
/
METABOLISMO
Año:
2020
Tipo del documento:
Article
País de afiliación:
Reino Unido