Somatostatin Inhibition of Pancreatic Glucagon Release from Monolayer Cultures and Interactions with Calcium

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Abstract
The effects of somatostatin (SRIF) on glucagon release were studied in the monolayer culture of newborn rat pancreas. SRIF inhibited glucagon release rapidly and in a dose dependent manner at concentrations of 1-1000 ng/ml. SRIF inhibited glucagon release under basal conditions and after stimulation by arginine, 3-isobutyl-1-methylxanthine (IBMX), high Ca++ concentrations, ionophore A23187 [2(3.beta., 9.alpha., 11.beta.-trimethyl)-8-(2-pyrrolecarboxymethyl)-1,7 dioxaspiro [6,6] undecyl-2.beta.-methyl-5-methylaminobenzoxazole-4-carboxylic acid], Ca++ and Ba++. SRIF inhibited ionophore-induced glucagon release over 60 min when a low concentration of A23187 was used (0.1 .mu.g/ml) but not when a high concentration (10 .mu.g/ml) was used. The stimulant effect of 10 .mu.g/ml A23187 was inhibited by SRIF during short periods of incubation. The percent inhibition of arginine-stimulated glucagon release due to SRIF remained unchanged when the Ca++ concentration in the medium was varied from 1-10 mM. SRIF promptly inhibits glucagon release under basal conditions or when stimulated by a variety of agents. The action of SRIF appears to be basic to the granule release process and not specifically antagonistic to any particular stimulants. Further, as SRIF inhibits release due to raised cytosol Ca++ (e.g., ionophore-Ca++ or high Ca++ experiments) the action is probably at a late point in the release mechanism.