Glucagonlike peptide I (7-37) actions on endocrine pancreas.
Glucagonlike peptide I (7-37) [GLP-I-(7-37)], encoded with glucagon and glucagonlike peptide II and intervening peptide II in the rat and human glucagon gene, is processed from proglucagon in both pancreas and intestine and is a potent stimulator of insulin secretion. Unequivocal insulin release from the isolated perfused rat pancreas is elicited by a 10(-11) M concentration of this peptide, and a weak response is found at 10(-12) M. We found that GLP-I-(7-37) is approximately 100 times more potent than glucagon in the stimulation of insulin secretion. Insulin release in response to GLP-I-(7-37) is highly dependent on the ambient glucose concentration; no response is detectable at a glucose concentration of 2.8 mM, and at 6.6 and 16.7 mM, insulin release is augmented by 4.7 and 22.8 ng/ml, respectively. The pattern of insulin secretion stimulated by GLP-I-(7-37) is biphasic, with an initial spike followed by a plateau of sustained release. The effects on insulin release of GLP-I-(7-36) amide, a GLP-I analogue, and GLP-I-(7-37) at concentrations of 10(-11) M were indistinguishable. We also found that GLP-I-(7-37) at 10(-9) M does not influence glucagon secretion and that glucagonlike peptide II and the intervening peptide II, two other peptides encoded by the glucagon gene, have no detectable effects on insulin secretion.
Weir
G C
GC
Joslin Diabetes Center, Boston, MA 02215.
Mojsov
S
S
Hendrick
G K
GK
Habener
J F
JF
D000818:Animals; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology; 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; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology*; D051381:Rats
D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose; C051322:glucagon-like peptide 1 (7-37)