Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36) amide in type 2 (noninsulin-dependent) diabetic patients.
The aim of the study was to investigate whether inhibition of gastric emptying of meals plays a role in the mechanism of the blood glucose-lowering action of glucagon-like peptide-1-(7-36) amide [GLP-1-(7-36) amide] in type 2 diabetes. Eight poorly controlled type 2 diabetic patients (age, 58 +/- 6 yr; body mass index, 30.0 +/- 5.2 kg/m2; hemoglobin A1c, 10.5 +/- 1.2%) were studied in the fasting state (plasma glucose, 11.1 +/- 1.1 mmol/L). A liquid meal of 400 mL containing 8% amino acids and 50 g sucrose (327 Kcal) was administered at time zero by a nasogastric tube. Gastric volume was determined by a dye dilution technique using phenol red. In randomized order, GLP-1-(7-36) amide (1.2 pmol/kg.min; Saxon Biochemicals) or placebo (0.9% NaCl with 1% human serum albumin) was infused between -30 and 240 min. In the control experiment, gastric emptying was completed within 120 min, and plasma glucose, insulin, C-peptide, GLP-1-(7-36) amide, and glucagon concentrations transiently increased. With exogenous GLP-1-(7-36) amide (plasma level, approximately 70 pmol/L), gastric volume remained constant over the period it was measured (120 min; P < 0.0001 vs. placebo), and plasma glucose fell to normal fasting values (5.4 +/- 0.7 mmol/L) within 3-4 h, whereas insulin was stimulated in most, but not all, patients, and glucagon remained at the basal level or was slightly suppressed. In conclusion, GLP-1-(7-36) amide inhibits gastric emptying in type 2 diabetic patients. Together with the stimulation of insulin and the inhibition of glucagon secretion, this effect probably contributes to the blood glucose-lowering action of GLP-1-(7-36) amide in type 2-diabetic patients when studied after meal ingestion. At the degree observed, inhibition of gastric emptying, however, must be overcome by tachyphylaxis, reduction in dose, or pharmacological interventions so as not to interfere with the therapeutic use of GLP-1-(7-36) amide in type 2 diabetic patients.
Willms
B
B
Fachklinik für Diabetes und Stoffwechselkrankheiten, Bad Lauterberg, Germany.
Werner
J
J
Holst
J J
JJ
Orskov
C
C
Creutzfeldt
W
W
Nauck
M A
MA
D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005746:Gastric Emptying; D005934:Glucagon / Q000097:blood / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology*; D011498:Protein Precursors / Q000097:blood / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon