Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP-1 [7-36 amide] after subcutaneous injection in healthy volunteers. Dose-response-relationships

Diabetologia. 1995 Jun;38(6):720-5. doi: 10.1007/BF00401846.

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)

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Mass Index
  • C-Peptide / blood
  • Dose-Response Relationship, Drug
  • Fasting
  • Female
  • Glucagon / blood
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Humans
  • Injections, Subcutaneous
  • Insulin / blood
  • Kinetics
  • Male
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacokinetics*
  • Peptide Fragments / pharmacology*
  • Random Allocation
  • Reference Values
  • Time Factors

Substances

  • Blood Glucose
  • C-Peptide
  • Insulin
  • Peptide Fragments
  • glucagon-like peptide 1 (7-36)amide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon