Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans.
Glucagon-like peptide 1 (GLP-1) has been shown to inhibit gastric emptying of liquid meals in type 2 diabetic patients. It was the aim of the present study to compare the action of physiological and pharmacological doses of intravenous GLP-1-(7-36) amide and GLP-1-(7-37) on gastric emptying in normal volunteers. Nine healthy subjects participated (26 +/- 3 yr; body mass index 22.9 +/- 1.6 kg/m2; hemoglobin A1C 5.0 +/- 0.2%) in five experiments on separate occasions after an overnight fast. A nasogastric tube was positioned for the determination of gastric volume by use of a dye-dilution technique (phenol red). GLP-1-(7-36) amide (0.4, 0.8, or 1.2 pmol.kg-1.min-1), GLP-1-(7-37) (1.2 pmol.kg-1.min-1), or placebo was infused intravenously from -30 to 240 min. A liquid meal (50 g sucrose, 8% amino acids, 440 ml, 327 kcal) was administered at 0 min. Glucose, insulin, and C-peptide were measured over 240 min. Gastric emptying was dose dependently slowed by GLP-1-(7-36) amide (P < 0.0001). Effects of GLP-1-(7-37) at 1.2 pmol.kg-1.min-1 were virtually identical. GLP.1 dose dependently stimulated fasting insulin secretion (-30 to 0 min) and slightly reduced glucose concentrations. After the meal (0-240 min), integrated incremental glucose (P < 0.0001) and insulin responses (P = 0.01) were reduced (dose dependently) rather than enhanced. In conclusion, 1) GLP-1-(7-36) amide or -(7-37) inhibits gastric emptying also in normal subjects, 2) physiological doses (0.4 pmol.kg-1.min-1) still have a significant effect, 3) despite the known insulinotropic actions of GLP-1-(7-36) amide and -(7-37), the net effect of administering GLP-1 with a meal is no change or a reduction in meal-related insulin responses. These findings suggest a primarily inhibitory function for GLP-1 (ileal brake mechanisms).
Nauck
M A
MA
Department of Medicine, Ruhr-University, Bochum, Germany.
Niedereichholz
U
U
Ettler
R
R
Holst
J J
JJ
Orskov
C
C
Ritzel
R
R
Schmiegel
W H
WH
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D004435:Eating; D005215:Fasting; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D010446:Peptide Fragments / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D010455:Peptides; D019518:Postprandial Period; D011498:Protein Precursors / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D012016:Reference Values; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C051322:glucagon-like peptide 1 (7-37)