Direct effect of GLP-1 infusion on endogenous glucose production in humans.
Diabetologia
; 56(1): 156-61, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-23064290
ABSTRACT
AIMS/HYPOTHESIS:
Glucagon-like peptide-1 (GLP-1) lowers glucose levels by potentiating glucose-induced insulin secretion and inhibiting glucagon release. The question of whether GLP-1 exerts direct effects on the liver, independently of the hormonal changes, is controversial. We tested whether an exogenous GLP-1 infusion, designed to achieve physiological postprandial levels, directly affects endogenous glucose production (EGP) under conditions mimicking the fasting state in diabetes.METHODS:
In 14 healthy volunteers, we applied the pancreatic clamp technique, whereby plasma insulin and glucagon levels are clamped using somatostatin and hormone replacement. The clamp was applied in paired, 4 h experiments, during which saline (control) or GLP-1(7-37)amide (0.4 pmol min⻹ kg⻹) was infused.RESULTS:
During the control study, plasma insulin and glucagon were maintained at basal levels and plasma C-peptide was suppressed, such that plasma glucose rose to a plateau of ~10.5 mmol/l and tracer-determined EGP increased by ~60%. During GLP-1 infusion at matched plasma glucose levels, the rise of EGP from baseline was fully prevented. Lipolysis (as indexed by NEFA concentrations and tracer-determined glycerol rate of appearance) and substrate utilisation (by indirect calorimetry) were similar between control and GLP-1 infusion. CONCLUSIONS/INTERPRETATION:
GLP-1 inhibits EGP under conditions where plasma insulin and glucagon are not allowed to change and glucose concentrations are matched, indicating either a direct effect on hepatocytes or neurally mediated inhibition.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Regulação para Cima
/
Peptídeo 1 Semelhante ao Glucagon
/
Gluconeogênese
/
Hipoglicemiantes
/
Fígado
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Female
/
Humans
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Male
Idioma:
En
Revista:
Diabetologia
Ano de publicação:
2013
Tipo de documento:
Article