GLP-1 does not not acutely affect insulin sensitivity in healthy man

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L Orskov, J J Holst, J Møller, C Orskov, N Møller, K G Alberti, O Schmitz

Previous studies have suggested that glucagon-like peptide-1 (GLP-1) (7-36 amide) may have the direct effect of increasing insulin sensitivity in healthy man. To evaluate this hypothesis we infused GLP-1 in seven lean healthy men during a hyper insulinaemic (0.8 mU.kg-1.min-1), euglycaemic (5 mmol/l) clamp. Somatostatin (450 micrograms/h was infused to suppress endogenous insulin secretion, and growth hormone (3 ng.kg-1.min-1) and glucagon (0.8 ng.kg-1.min-1) were infused to maintain basal levels. GLP-1 (50 pmol.kg-1.h-1) or 154 mmol/l NaCl (placebo) was infused after 3 h of equilibration, i.e. from 180-360 min. GLP-1 infusion resulted in GLP-1 levels of approximately 40 pmol/l. Plasma glucose, insulin, growth hormone, and glucagon levels were similar throughout the clamps. The rate of glucose infusion required to maintain euglycaemia was similar with or without GLP-1 infusion (7.69 +/- 1.17 vs 7.76 +/- 0.95 mg kg-1.min-1 at 150-180 min and 8.56 +/- 1.13 vs 8.55 +/- 0.68 mg.kg-1.min-1 at 330-360 min) and there was no difference in isotopically determined hepatic glucose production rates (-0.30 +/- 0.23 vs -0.16 +/- 0.22 mg.kg-1.min-1 at 330-360 min). Furthermore, arteriovenous glucose differences across the forearm were similar with or without GLP-1 infusion (1.43 +/- 0.23 vs 1.8 +/- 0.29 mmol/l), (ANOVA; p > 0.60, in all instances). In conclusion, GLP-1 (7-36 amide) administered for 3 h, leading to circulating levels within the physiological range, does not affect insulin sensitivity in healthy man.

Original languageEnglish
JournalDiabetologia
Volume39
Issue number10
Pages (from-to)1227-32
Number of pages6
ISSN0012-186X
Publication statusPublished - Oct 1996

    Research areas

  • 3-Hydroxybutyric Acid, Adult, Alanine/blood, Analysis of Variance, Blood Glucose/drug effects, C-Peptide/blood, Calorimetry, Indirect, Fatty Acids, Nonesterified/blood, Glucagon/blood, Glucagon-Like Peptide 1, Glucagon-Like Peptides, Glucose Clamp Technique, Humans, Hydroxybutyrates/blood, Infusions, Intravenous, Insulin/blood, Lactates/blood, Male, Neurotransmitter Agents/pharmacology, Peptide Fragments/administration & dosage, Reference Values, Somatostatin/administration & dosage, Time Factors

ID: 194815463