Effect of octreotide on stimulated insulin release from pancreatic tissue slices.
This study was designed to investigate a possible mechanism of action by which octreotide acetate causes insulin suppression in the denervated pancreas. Canine tissue slices were placed in a pH-adjusted medium with varying concentrations of glucose and octreotide acetate: Experiment 1, 30 min in basal medium with 0.6 mg/ml glucose; Experiment 2, addition of 6.0 mg/ml glucose; Experiment 3, addition of 4 microg octreotide acetate/70 ml (comparable to 100 microg/25 kg body weight); Experiment 4, addition of 16 microg octreotide acetate/70 ml; Experiment 5, incubation with 6.0 mg glucose/ml and 4 microg octreotide acetate/70 ml; Experiment 6, incubation with 6.0 mg glucose/ml and 16 microg octreotide acetate/70 ml; Experiment 7, preincubation with 4 microg octreotide acetate/70 ml, then with 6.0 mg glucose/ml; and Experiment 8, preincubation with 16 microg octreotide acetate/70 ml, then with 6.0 mg glucose/ml. Medium levels of insulin, glucagon, and amylase were collected at intervals during the incubation periods. There was an appropriate increase in the rate of insulin release to glucose stimulation in the high-glucose (6.0 mg/ml) group. There was no significant inhibition of basal or glucose-stimulated insulin release with either simultaneous or pretreatment of the canine pancreatic tissue slices with either concentration of octreotide acetate. These studies support an indirect mechanism by which octreotide acetate exerts its inhibitory effect on endocrine and exocrine function in the canine pancreas transplant model.
Presti
M E
ME
Department of Internal Medicine, Saint Louis University Health Sciences Center, Missouri 63110-0250, USA.
Burton
F R
FR
Niehoff
M L
ML
Rioux
J
J
Garvin
P J
PJ
D000681:Amylases / Q000378:metabolism; D000818:Animals; D004285:Dogs; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D015282:Octreotide / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D012844:Sincalide
D005765:Gastrointestinal Agents; D007328:Insulin; D005934:Glucagon; D000681:Amylases; D005947:Glucose; D012844:Sincalide; D015282:Octreotide