Hepatic portal vein denervation impairs oral glucose tolerance but not exenatide's effect on glycemia.
Am J Physiol Endocrinol Metab
; 307(8): E644-52, 2014 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-25117408
ABSTRACT
The hepatoportal area is an important glucohomeostatic metabolic sensor, sensing hypoglycemia, hyperglycemia, and hormones such as glucagon-like peptide-1 (GLP-1). We have reported previously that activation of hepatoportal sensors by intraportal infusion of glucose and GLP-1 or by subcutaneous administration of GLP-1 receptor activator exenatide and of intraportal glucose improved glycemia independent of corresponding changes in pancreatic hormones. It is not clear whether this effect is mediated via the portal vein (PV) or by direct action on the liver itself. To test whether receptors in the PV mediate exenatide's beneficial effect on glucose tolerance, we performed 1) paired oral glucose tolerance tests (OGTT) with and without exenatide and 2) intravenous glucose tolerance tests before and after PV denervation in canines. Denervation of the portal vein affected oral glucose tolerance; post-denervation (POST-DEN) OGTT glucose and insulin AUC were 50% higher than before denervation (P = 0.01). However, portal denervation did not impair exenatide's effect to improve oral glucose tolerance (exenatide effect 48 ± 12 mmol·l⻹·min before vs. 64 ± 26 mmol·l⻹·min after, P = 0.67). There were no changes in insulin sensitivity or secretion during IVGTTs. Portal vein sensing might play a role in controlling oral glucose tolerance during physiological conditions but not in pharmacological activation of GLP-1 receptors by exenatide.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Veia Porta
/
Peçonhas
/
Receptores de Glucagon
/
Intolerância à Glucose
/
Hiperglicemia
/
Hipoglicemiantes
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Endocrinol Metab
Assunto da revista:
ENDOCRINOLOGIA
/
FISIOLOGIA
/
METABOLISMO
Ano de publicação:
2014
Tipo de documento:
Article