Effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-I-(7-36) on insulin secretion.
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP)-I-(7-36) are probably the most important "incretins," but there is controversy as to their relative insulinotropic activities. The effects of natural (np) and synthetic porcine (sp) GIP, synthetic human (sh) GIP, and GLP-I-(7-36) on insulin secretion from the perfused rat pancreas were compared using gradient perfusion. Insulin secretion was increased by both spGIP and GLP-I-(7-36) at concentrations of approximately 16 pM. Maximal responses to GLP-I-(7-36) in the presence of 16.7 mM glucose were slightly greater than with npGIP or spGIP, but with 10 mM glucose spGIP and GLP-I-(7-36) exerted equivalent effects. Responses to shGIP were greatly reduced compared with spGIP. In the presence of 50 pM spGIP or GLP-I-(7-36) the glucose threshold was 4.5 +/- 0.11 mM. The data indicate that GLP-I-(7-36) and porcine GIP are equally insulinotropic and share the same glucose threshold for activity, whereas shGIP is less active. At the concentrations found postprandially, however, GIP is likely to be the more important incretin.
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Department of Physiology, University of British Columbia, Vancouver, Canada.
Brown
J C
JC
Ma
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P
Pederson
R A
RA
McIntosh
C H
CH
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005749:Gastric Inhibitory Polypeptide / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
D007328:Insulin; D010446:Peptide Fragments; C061970:glucagon-like peptide 1 (7-36); C055453:glucagon-like peptide 1 (7-36)amide; D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose