Glucagon-like peptide-1 is a physiological incretin in rat.
Glucagon-like peptide-1 7-36 amide (GLP-1) has been postulated to be the primary hormonal mediator of the entero-insular axis but evidence has been indirect. The discovery of exendin (9-39), a GLP-1 receptor antagonist, allowed this to be further investigated. The IC50 for GLP-1 receptor binding, using RIN 5AH beta-cell membranes, was found to be 0.36 nmol/l for GLP-1 and 3.44 nmol/l for exendin (9-39). There was no competition by exendin (9-39) at binding sites for glucagon or related peptides. In the anaesthetized fasted rat, insulin release after four doses of GLP-1 (0.1, 0.2, 0.3, and 0.4 nmol/kg) was tested by a 2-min intravenous infusion. Exendin (9-39) (1.5, 3.0, and 4.5 nmol/kg) was administered with GLP-1 0.3 nmol/kg, or saline, and only the highest dose fully inhibited insulin release. Exendin (9-39) at 4.5 nmol/kg had no effect on glucose, arginine, vasoactive intestinal peptide or glucose-dependent insulinotropic peptide stimulated insulin secretion. Postprandial insulin release was studied in conditioned conscious rats after a standard meal. Exendin (9-39) (0.5 nmol/kg) considerably reduced postprandial insulin concentrations, for example by 48% at 15 min (431 +/- 21 pmol/l saline, 224 +/- 32 pmol/l exendin, P < 0.001). Thus, GLP-1 appears to play a major role in the entero-insular axis.
Wang
Z
Z
Division of Endocrinology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Wang
R M
RM
Owji
A A
AA
Smith
D M
DM
Ghatei
M A
MA
Bloom
S R
SR
D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002478:Cells, Cultured; D003243:Consciousness; D004435:Eating; D005215:Fasting; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology; D005934:Glucagon / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000494:pharmacology; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology*; D010455:Peptides / Q000502:physiology*; D011498:Protein Precursors / Q000502:physiology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D018027:Receptors, Glucagon; C055453:glucagon-like peptide 1 (7-36)amide; D014660:Vasoactive Intestinal Peptide; C083773:exendin (9-39); D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D001120:Arginine; D005947:Glucose