The processing intermediate of human amylin, pro-amylin(1-48), has in vivo and in vitro bioactivity.
Biophys Chem
; 308: 107201, 2024 May.
Article
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| MEDLINE
| ID: mdl-38452520
ABSTRACT
Amylin is released by pancreatic beta-cells in response to a meal and its major soluble mature form (37 amino acid-peptide) produces its biological effects by activating amylin receptors. Amylin is derived from larger propeptides that are processed within the synthesizing beta-cell. There are suggestions that a partially processed form, pro-amylin(1-48) is also secreted. We tested the hypothesis that pro-amylin(1-48) has biological activity and that human pro-amylin(1-48) may also form toxic pre-amyloid species. Amyloid formation, the ability to cross-seed and in vitro toxicity were similar between human pro-amylin(1-48) and amylin. Human pro-amylin(1-48) was active at amylin-responsive receptors, though its potency was reduced at rat, but not human amylin receptors. Pro-amylin(1-48) was able to promote anorexia by activating neurons of the area postrema, amylin's primary site of action, indicating that amylin can tolerate significant additions at the N-terminus without losing bioactivity. Our studies help to shed light on the possible roles of pro-amylin(1-48) which may be relevant for the development of future amylin-based drugs.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Polipéptido Amiloide de los Islotes Pancreáticos
/
Amiloide
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biophys Chem
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suiza