Document Detail

Effect of L-364,718 on pancreatic endocrine function following partial pancreatectomy.
MedLine Citation:
PMID:  8812629     Owner:  NLM     Status:  MEDLINE    
This study was designed to determine the effect of a potent cholecystokinin antagonist, L-364,718, on canine pancreatic endocrine function following partial pancreatectomy. Plasma glucose, insulin, and glucagon were determined over a 2-hr interval following an intravenous bolus of 0.5 g/kg glucose in a 50% solution. The following groups were established: normal animals (group A, n = 5), normal animals pretreated with 20 nmole/kg L-364,178 (group B, n = 5), partially pancreatectomized animals (group C, n = 5), and partially pancreatectomized animals pretreated with 20 nmole/kg L-364,178 (group D, n = 5). In contrast to animals with an intact pancreas, pretreatment with L-364,718 following partial pancreatectomy resulted in a significant decrease in peak insulin (group C = 132.8 +/- 13.0 microU/ml vs Group D = 90.4 +/- 16.1 microU/ml, P < 0.05) and the basal-to-peak insulin difference (group C = 111.9 +/- 11.5 microU/ml vs group D = 77.5 +/- 16.6 microU/ml, P < 0.05). Despite this, the rate of glucose utilization (K value) was significantly increased in the partially pancreatectomized animals given the antagonist (group C = -1.22 +/- 0.22%/min vs group D = -2.79 +/- 0.427%/min) and there were no significant differences in basal or peak glucose when comparing the groups given L-364,718 with the groups given placebo (group A vs B and group C vs D). Thus, the CCK antagonist L-364,718 significantly decreases peak insulin in partially pancreatectomized animals but not in nonoperative control animals. There is a paradoxical increase in the rate of glucose utilization but no effect on glucose homeostasis. The effect of this antagonist in other models of reduced islet cell reserve (i.e., pancreas transplantation) remains to be determined.
M E Presti; M L Niehoff; F R Burton; H Solomon; P J Garvin
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of surgical research     Volume:  64     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1996-10-21     Completed Date:  1996-10-21     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  170-5     Citation Subset:  IM    
Department of Surgery, St. Louis University Health Sciences Center, St. Louis, Missouri 63110-0250, USA.
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MeSH Terms
Benzodiazepinones / pharmacology*
Blood Glucose / drug effects
Cell Count
Glucagon / blood
Glucose / metabolism
Hormone Antagonists / pharmacology*
Insulin / blood
Islets of Langerhans / cytology
Pancreas / cytology,  drug effects*,  surgery
Receptor, Cholecystokinin A
Receptors, Cholecystokinin / antagonists & inhibitors
Reg. No./Substance:
0/Benzodiazepinones; 0/Blood Glucose; 0/Hormone Antagonists; 0/Receptor, Cholecystokinin A; 0/Receptors, Cholecystokinin; 103420-77-5/Devazepide; 11061-68-0/Insulin; 50-99-7/Glucose; 9007-92-5/Glucagon

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