Glucagon receptor knockout mice display increased insulin sensitivity and impaired beta-cell function.
Diabetes
; 55(12): 3463-9, 2006 Dec.
Article
en En
| MEDLINE
| ID: mdl-17130493
ABSTRACT
In previous studies, glucagon receptor knockout mice (Gcgr(-/-)) display reduced blood glucose and increased glucose tolerance, with hyperglucagonemia and increased levels of glucagon-like peptide (GLP)-1. However, the role of glucagon receptor signaling for the regulation of islet function and insulin sensitivity is unknown. We therefore explored beta-cell function and insulin sensitivity in Gcgr(-/-) and wild-type mice. The steady-state glucose infusion rate during hyperinsulinemic-euglycemic clamp was elevated in Gcgr(-/-) mice, indicating enhanced insulin sensitivity. Furthermore, the acute insulin response (AIR) to intravenous glucose was higher in Gcgr(-/-) mice. The augmented AIR to glucose was blunted by the GLP-1 receptor antagonist, exendin-3. In contrast, AIR to intravenous administration of other secretagogues was either not affected (carbachol) or significantly reduced (arginine, cholecystokinin octapeptide) in Gcgr(-/-) mice. In islets isolated from Gcgr(-/-) mice, the insulin responses to glucose and several insulin secretagogues were all significantly blunted compared with wild-type mice. Furthermore, glucose oxidation was reduced in islets from Gcgr(-/-) mice. In conclusion, the present study shows that glucagon signaling is required for normal beta-cell function and that insulin action is improved when disrupting the signal. In vivo, augmented GLP-1 levels compensate for the impaired beta-cell function in Gcgr(-/-) mice.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Glucagón
/
Células Secretoras de Insulina
/
Insulina
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
Diabetes
Año:
2006
Tipo del documento:
Article
País de afiliación:
Dinamarca