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Diabetologia. 2013 Jan;56(1):156-61. doi: 10.1007/s00125-012-2738-3. Epub 2012 Oct 12.

Direct effect of GLP-1 infusion on endogenous glucose production in humans.

Author information

1
Department of Internal Medicine, University of Pisa School of Medicine, Via Roma, 67, 56100 Pisa, Italy.

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⁻¹ kg⁻¹) 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.

PMID:
23064290
DOI:
10.1007/s00125-012-2738-3
[Indexed for MEDLINE]
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