Insulinotropic effects of cholecystokinin, gastric inhibitory polypeptide and glucagon-like peptide-1 during perifusion of short-term cultured canine isolated islets.
Recent metabolic studies suggest that the incretin effect of gut hormones may account for most of the circulating insulin during mild postprandial hyperglycemia after transplantation of isolated islets. As yet, however, insulinotropic effects of pharmacological rather than physiological levels of the incretin candidates cholecystokinin-33 (CCK-33), gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) on isolated perifused islets have been reported. We examined the insulinotropic effects of these peptides during perifusion of canine isolated islets. Exploration of beta-cell sensitivity in our model with graded 0.1-10 nM doses of CCK-33 and GIP at a 7.5 mM glucose level demonstrated insulinotropic effects from the lowest level. We, therefore, focused on the (near-) physiological effects of both CCK-33 (20 pM), GIP (500 pM), and GLP-1 (100 pM) during perifusion at a 2.5, 7.5, and 10 mM glucose level. No effects of CCK-33 were observed. GIP enhanced insulin release 1.1- and 1.2-fold, at the 7.5 and 10 mM glucose level, respectively. GLP-1 stimulated insulin output from the 2.5 mM glucose level; and a maximum, 2-fold, increase of insulin output was observed from the 7.5 mM glucose level. Thus, isolated perifused islets do respond to near-physiological beta-cell stimulation with gut hormones, and both GIP and GLP-1 may contribute to a hyperglycemia-enhanced activation of the enteroinsular axis after transplantation of isolated islets.
van der Burg
M P
MP
Department of Surgery, University Hospital, Leiden, Netherlands. MvdBurg@RULLF2.MedFac.LeidenUniv.NL
Guicherit
O R
OR
Frölich
M
M
Gooszen
H G
HG
D000818:Animals; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology*
D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; C055453:glucagon-like peptide 1 (7-36)amide; D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002766:Cholecystokinin; D005947:Glucose