Interaction of glucagon-like peptide-1(7-36) amide and gastric inhibitory polypeptide or cholecystokinin on insulin and glucagon secretion from the isolated perfused rat pancreas.
The interaction of three incretin candidates, glucagon-like peptide-1(7-36)amide (t-GLP-1), gastric inhibitory polypeptide (GIP), and sulfated COOH-terminal octapeptide of cholecystokinin (CCK-8-S), on insulin and glucagon release from the isolated perfused rat pancreas was studied. Under the perfusate condition of 8.3 mmol/L glucose, coinfusion of 0.1 nmol/L t-GLP-1 and 0.1 nmol/L GIP resulted in an augmented insulin release greater than that obtained by the same dose of each peptide alone. The degree of stimulation elicited by t-GLP-1 and GIP reached a plateau at 0.3 nmol/L for both infusates, and no cooperative effect was observed by coinfusion at 0.3 nmol/L. Coinfusion of 0.1 nmol/L t-GLP-1 and and 0.1 nmol/L CCK-8-S also resulted in an augmented insulin release greater than that obtained by the same dose of each peptide alone. A similar cooperative effect was observed by coinfusion at 0.3 nmol/L, 1 nmol/L, and 3 nmol/L. With the same perfusion experiments, glucagon release was not significantly affected by any peptide at concentrations of 0.1, 0.3, 1, or 3 nmol/L. The coinfusion of 1 nmol/L t-GLP-1 and GIP elicited a transient, but significant, increase in glucagon release. A similar result was obtained by the coinfusion of 0.3 nmol/L and 3 nmol/L t-GLP-1 and GIP, respectively. The coinfusion of t-GLP-1 and CCK-8-S did not affect the glucagon release.(ABSTRACT TRUNCATED AT 250 WORDS)
Suzuki
S
S
Department of Internal Medicine, University of Tsukuba, Japan.
Kawai
K
K
Ohashi
S
S
Watanabe
Y
Y
Yamashita
K
K
D000818:Animals; D004347:Drug Interactions; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology*; D013997:Time Factors
D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; C061970:glucagon-like peptide 1 (7-36); D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D012844:Sincalide