Influence of glucagon-like peptide-1 on beta cell responsiveness.
The postulated incretin factor glucagon-like peptide-1 (GLP-1) causes a glucose-dependent increase in insulin secretion from perifused rat islets. In the presence of 6 mM glucose the response to 10 nM GLP-1 is characterized by a large initial spike of secretion, followed by a brief, slowly rising phase. However, after 30-40 min of stimulation, this phase subsides to prestimulatory secretory rates. Raising the glucose level to 8 mM, however, amplifies and sustains the stimulatory effect of 10 nM GLP-1. The response to GLP-1 (10 nM) in the presence of 8 mM glucose is abolished by the metabolic inhibitor mannoheptulose (15 mM), and reduced by the calcium channel antagonist nitrendipine (5 microM), or the protein kinase C inhibitor of staurosporine (20 nM). A significant synergistic effect of GLP-1 (10 nM) and 10 microM carbachol, a cholinergic agonist, on insulin secretion was observed in the presence of 6 mM glucose. In the presence of either 6 or 8 mM glucose, GLP-1 (10 nM) has no significant effect on glucose usage or on inositol phosphate generation in [3H]inositol prelabeled islets. The results support the concept that GLP-1 may function as an important physiologic incretin factor, particularly when accompanied by agonists that activate phosphoinositide hydrolysis.
Zawalich
W S
WS
Yale University School of Nursing, New Haven, CT 06536-0740.
Zawalich
K C
KC
Rasmussen
H
H
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology* / Q000502:physiology; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008356:Mannoheptulose / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011498:Protein Precursors / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D005749:Gastric Inhibitory Polypeptide; D008356:Mannoheptulose; D052216:Glucagon-Like Peptide 1; D002217:Carbachol; D005934:Glucagon; D002766:Cholecystokinin; D005947:Glucose