Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase ß-cell mass in fetal sheep.
Am J Physiol Endocrinol Metab
; 304(4): E352-62, 2013 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-23211516
ABSTRACT
Amino acids and glucose acutely stimulate fetal insulin secretion. In isolated adult pancreatic islets, amino acids potentiate glucose-stimulated insulin secretion (GSIS), but whether amino acids have this same effect in the fetus is unknown. Therefore, we tested the effects of increased fetal amino acid supply on GSIS and morphology of the pancreas. We hypothesized that increasing fetal amino acid supply would potentiate GSIS. Singleton fetal sheep received a direct intravenous infusion of an amino acid mixture (AA) or saline (CON) for 10-14 days during late gestation to target a 25-50% increase in fetal branched-chain amino acids (BCAA). Early-phase GSIS increased 150% in the AA group (P < 0.01), and this difference was sustained for the duration of the hyperglycemic clamp (105 min) (P < 0.05). Glucose-potentiated arginine-stimulated insulin secretion (ASIS), pancreatic insulin content, and pancreatic glucagon content were similar between groups. ß-Cell mass and area were unchanged between groups. Baseline and arginine-stimulated glucagon concentrations were increased in the AA group (P < 0.05). Pancreatic α-cell mass and area were unchanged. Fetal and pancreatic weights were similar. We conclude that a sustained increase of amino acid supply to the normally growing late-gestation fetus potentiated fetal GSIS but did not affect the morphology or insulin content of the pancreas. We speculate that increased ß-cell responsiveness (insulin secretion) following increased amino acid supply may be due to increased generation of secondary messengers in the ß-cell. This may be enhanced by the paracrine action of glucagon on the ß-cell.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pâncreas
/
Células Secretoras de Insulina
/
Aminoácidos
/
Glucose
/
Insulina
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Am J Physiol Endocrinol Metab
Assunto da revista:
ENDOCRINOLOGIA
/
FISIOLOGIA
/
METABOLISMO
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos