title: Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP-1 [7-36 amide] after subcutaneous injection in healthy volunteers. Dose-response-relationships.
abstract: Intravenous infusions of glucagon-like peptide 1 (GLP-1) [7-36 amide] are glucose-dependently insulinotropic and glucagonostatic and normalize plasma glucose concentrations in non-insulin-dependent diabetic patients. It was the aim of this study to investigate whether subcutaneous GLP-1 [7-36 amide] also has an influence on insulin and glucagon secretion, and which doses are required for significant effects. Therefore, eight healthy volunteers (24 +/- 2 years, body mass index [BMI] 21.9 +/- 2.3 kg/m2) were studied in the fasting state on five occasions in randomized order. Placebo (0.9% NaCl with 1% human serum albumin) or GLP-1 [7-36 amide] in doses of 0.15, 0.5, 1.5 or 4.5 nmol/kg body weight (volume 1 ml or, at the highest dose, 2 ml) was administered subcutaneously. An intravenous glucose bolus (0.33 g/kg body weight) was injected 30 min later. Blood was drawn for the measurement of glucose, insulin, C-peptide, GLP-1 [7-36 amide], and glucagon using specific radioimmunoassays. There were dose-related increments in GLP-1 [7-36 amide] concentrations (p < 0.0001). However, basal values were reached again after 90-120 min. Before glucose administration, insulin (p < 0.0001) and C-peptide (p < 0.0004) increased, whereas glucagon (p = 0.0018) and glucose (p < 0.0001) decreased in a dose-dependent manner. After glucose stimulation, integrated increments in insulin (p = 0.0007) and C-peptide (p = 0.02) were augmented and kG-values increased (p < 0.0001) in a dose-related fashion. The extent of reactive hypoglycaemia was related to the GLP-1 [7-36 amide] dose.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Ruhr-University Bochum, Knappschafts-Krankenhaus, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Ritzel
authors.forename: C
authors.initials: C
authors.lastname: Orskov
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: M A
authors.initials: MA
authors.lastname: Nauck
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011897:Random Allocation; D012016:Reference Values; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon