Biological Effects and Metabolic Rates of Glucagonlike Peptide-1 7–36 Amide and Glucagonlike Peptide-1 7–37 in Healthy Subjects Are Indistinguishable

Abstract

The biological effects and the metabolism of the intestinal hormone glucagonlike peptide-1 7–36 amide and glucagonlike peptide-1 7–37 were studied in normal healthy subjects. GLP-1 7–36 amide and GLP-1 7–37 equipotently stimulated insulin secretion (integrated hormone response 0–60 min, 631 ± 211 vs. 483 ± 177 pmol/h × L⁻¹) and C-peptide secretion (integrated hormone response 9064 ± 1804 vs. 9954 ± 2031 pmol/h × L⁻¹) and equipotently lowered plasma glucose (integrated decrease 48.3 ± 5.7 vs. 46.2 ± 8.4 mmol/h × L-1) and plasma glucagon (integrated decrease 80.4 ± 24.3 vs. 156.0 ± 34.6 pmol/h × L⁻¹). Both GLP-1 7–36 amide and GLP-1 7–37 lowered the plasma concentration of free fatty acids significantly. The plasma half-lives of GLP-1 7–36 amide and GLP-1 7–37 were 5.3 ± 0.4 vs. 6.1 ± 0.8 min, and the metabolic clearance rates of the two peptides also were similar (14.6 ± 2.4 vs. 12.2 ± 1.0 pmol/kg × min). In conclusion, COOH-terminal amidation is neither important for the metabolism of GLP-1 nor for its effects on the endocrine pancreas.