GLP-1 does not not acutely affect insulin sensitivity in healthy man.
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.
Institute of Experimental Clinical Research Arhus University Hospital, Denmark.
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Orskov
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Holst
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Møller
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Orskov
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Møller
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Alberti
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Schmitz
D020155:3-Hydroxybutyric Acid; D000328:Adult; D000409:Alanine / Q000097:blood; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D002153:Calorimetry, Indirect; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D015309:Glucose Clamp Technique; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D000078790:Insulin Secretion; D007773:Lactates / Q000097:blood; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values; D013004:Somatostatin / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D007773:Lactates; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; D013004:Somatostatin; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000409:Alanine; D020155:3-Hydroxybutyric Acid