Effects of glucagonlike peptide I-(7-36) on release of insulin, glucagon, and somatostatin by rat pancreatic islet cell monolayer cultures.
Glucagonlike peptide I (GLP-I-(7-36] is cleaved from proglucagon in ileal epithelial cells and increases in human plasma after nutrient ingestion. This peptide has been shown to stimulate insulin secretion in vitro and in vivo and thus potentially acts as an incretin. To characterize its action on islet cells, the release of insulin, glucagon, and somatostatin by rat pancreatic islet monolayer cultures at varying concentrations of GLP-I-(7-36) was measured. The interaction of GLP-I-(7-36) with nutrient substrates was assessed by adding amino acids and differing glucose concentrations to the cultures. Islet cell cultures (n = 5) were incubated for 1 h in medium containing 1.67 or 16.7 mM glucose or 1.67 mM glucose supplemented with amino acids and GLP-I-(7-36) at 10(-13)-10(-7) M. Hormone release was compared with control cultures containing no GLP-I-(7-36); 1.67-16.7 mM glucose with and without GLP-I-(7-36) at 10(-11) M; and 1.67, 3.3, 8.3, or 11.1 mM glucose alone or supplemented with amino acids, GLP-I-(7-36) 10(-11) M, or both amino acids and GLP-I-(7-36). In medium with 1.67 or 16.7 mM glucose or 1.67 mM glucose and amino acids, GLP-I-(7-36) increased insulin secretion two- to threefold over control at concentrations of 10(-9), 10(-11), and 10(-12) M, respectively. In medium with increasing concentrations of glucose, GLP-I-(7-36) at 10(-11) M significantly increased insulin secretion at glucose concentrations greater than or equal to 3.34 mM.(ABSTRACT TRUNCATED AT 250 WORDS)
D'Alessio
D A
DA
Department of Medicine, University of Washington, Seattle 98195.
Fujimoto
W Y
WY
Ensinck
J W
JW
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism*
D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; C061970:glucagon-like peptide 1 (7-36); D013004:Somatostatin; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose