Tigerinin-1R: a potent, non-toxic insulin-releasing peptide isolated from the skin of the Asian frog, Hoplobatrachus rugulosus.
Diabetes Obes Metab
; 13(12): 1114-22, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-21736689
ABSTRACT
AIM:
Characterization of peptides in the skin of the Vietnamese common lowland frog Hoplobatrachus rugulosus with the ability to stimulate insulin release in vitro and improve glucose tolerance in vivo.METHODS:
Peptides in an extract of skin were purified by reversed-phase HPLC, and their abilities to stimulate the release of insulin and the cytosolic enzyme lactate dehydrogenase were determined using BRIN-BD11 clonal ß cells. Insulin-releasing potencies of synthetic peptides and their effects on membrane potential and intracellular Ca²âº concentration were also measured using BRIN-BD11 cells. Effects on glucose tolerance and insulin release in vivo were determined in mice fed a high-fat diet to induce obesity and insulin resistance.RESULTS:
A cyclic dodecapeptide (RVCSAIPLPICH.NH2), termed tigerinin-1R, was isolated from the skin extract that lacked short-term cytotoxic and haemolytic activity but significantly (p < 0.01) stimulated the rate of release of insulin from BRIN-BD11 cells at concentrations ≥ 0.1 nM. The maximum response was 405% of the basal rate at 5.6 mM ambient glucose concentration and 290% of basal rate at 16.7 mM glucose. C-terminal α-amidation was necessary for high potency and a possible mechanism of action of the peptide-involved membrane depolarization and an increase in intracellular Ca²âº concentration. Administration of tigerinin-1R (75 nmol/kg body weight) to high fat-fed mice significantly (p < 0.05) enhanced insulin release and improved glucose tolerance during the 60-min period following an intraperitoneal glucose load.CONCLUSION:
Tigerinin-1R is a potent, non-toxic insulin-releasing peptide that shows potential for development into an agent for the treatment of type 2 diabetes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Pele
/
Proteínas de Anfíbios
/
Diabetes Mellitus Tipo 2
/
Peptídeo 1 Semelhante ao Glucagon
/
Insulina
Limite:
Animals
Idioma:
En
Revista:
Diabetes Obes Metab
Assunto da revista:
ENDOCRINOLOGIA
/
METABOLISMO
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Reino Unido