Characterization of the inhibitory effect of somatostatin upon insulin and glucagon release in the isolated perfused canine pancreas: evidence for interaction with calcium.
Somatostatin is a potent inhibitor of insulin and glucagon release from the isolated perfused canine pancreas. The present investigation was undertaken to characterize the pancreatic effects of somatostatin by studying its ability to influence insulin and glucagon release from the same perfusion preparation in response to various well-known stimuli and modulators. Somatostatin inhibited insulin and glucagon release in all test situations chosen but one. Thus, somatostatin inhibits pancreatic hormone secretion irrespective of whether it is modulated by (1) a primary initiator of insulin release--glucose (1.3 or 8.3 mM), leucine (4.1 mM), tolbutamide (2.6 mM); (2) a potentiator of insulin release, i.e., a substance that requires the presence of glucose--arginine (1 mM); (3) substances known to increase the level of cyclic AMP (cAMP) in the islets--glucagon (2 ng/ml), cAMP (1 mM), theophylline (1 mM); (4) an autonomic agent--epinephrine (2 ng/ml), acetylcholine (10 microM); or (5) alpha and beta adrenergic antagonists--phentolamine (1 microM), propranolol (1 microM). In contrast, high Ca++ concentrations (4.8 and 8.2 mM) abolished the inhibitory action of somatostatin on both insulin and glucagon release. These findings lend support to the hypothesis that somatostatin acts at a stage of secretory processes, possibly related to Ca++ inactivation, late in the chain of events leading to hormone release.
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007930:Leucine / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology*; D013565:Sympatholytics / Q000494:pharmacology
D006727:Hormone Antagonists; D007328:Insulin; D013565:Sympatholytics; D013004:Somatostatin; D005934:Glucagon; D001120:Arginine; D000242:Cyclic AMP; D007930:Leucine; D005947:Glucose; D002118:Calcium; D004837:Epinephrine