Gene/Protein
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Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
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Query: UMLS:C0011849 (
diabetes
)
277,896
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The influence of
L 364718
on islet responsiveness to sulfated cholecystokinin (CCK-8S) was investigated. In islets whose inositol-containing phospholipids were prelabeled during a 2-h incubation period, subsequent exposure to
L 364718
(1 nM) significantly impaired the secretion of insulin usually noted in response to 200 nM CCK-8S in the simultaneous presence of 7 mM glucose. A higher level of the antagonist (10 nM) completely abolished insulin secretion.
L 364718
(1-10 nM) reduced the efflux of 3H from myo-[2-3H]-inositol prelabeled islets in parallel with the reduction in secretion.
L 364718
(10 nM) significantly reduced the accumulation of 3H-containing inositol phosphates usually noted with CCK-8S addition.
L 364718
, at levels 10- to 100-fold greater than those necessary to attenuate CCK-8S-induced insulin secretion, had no adverse effect on the insulin secretory response of freshly isolated islets to 10 mM glucose alone, 5 mM D-glyceraldehyde, 15 mM alpha-ketoisocaproate, or 50 ng/ml gastric inhibitory polypeptide.
L 364718
(1000 nM) had no adverse influence on carbamylcholine (1 mM)-induced phosphoinositide hydrolysis. These results establish
L 364718
as a potent and highly selective antagonist of cholecystokinin's stimulatory actions on beta-cells. Because of its potency, selectivity, and oral effectiveness, in vivo studies with
L 364718
, aimed at unraveling the pleiotropic effects of CCK-8S on glucose and insulin homeostasis, seem feasible.
Diabetes
1988 Oct
PMID:Stimulatory effects of cholecystokinin on isolated perifused islets inhibited by potent and specific antagonist L 364718 [corrected]. 304 73
It has been suggested that the gut hormone cholecystokinin (CCK), by modulating insulin output from pancreatic beta-cells, plays an important role in the enteroinsular axis. To investigate this hypothesis, eight rats were studied on two different occasions: after injection of
L 364718
, a specific antagonist of CCK binding to its membrane receptor, and after vehicle injection. In both studies a mixture of casein (11%) and glucose (9%) was infused through a chronic indwelling intraduodenal catheter to evoke CCK secretion. Plasma was analyzed for insulin, glucose, glucagon, and tyrosine many times during the procedure. Prior administration of the CCK antagonist significantly attenuated the increase in plasma insulin and glucagon after casein infusion. These results support the concept that cholecystokinin plays an important physiologic role in the in vivo regulation of postprandial plasma insulin and glucagon concentrations after protein ingestion.
Diabetes
1987 Oct
PMID:Physiological role of cholecystokinin in meal-induced insulin secretion in conscious rats. Studies with L 364718, a specific inhibitor of CCK-receptor binding. 330 89
