Inhibition by Somatostatin of Glucagon-Induced Glucose Release from the Isolated Perfused Rat Liver

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Abstract
Livers from fed rats (140-160 g) were perfused in situ with a non-recycled, semi-synthetic, erythrocyte-containing medium to determine whether synthetic cyclic [c] somatostatin directly inhibited glucagon-stimulated glucose release into the effluent. Hepatic glucose release was measured by the increase (or in some instances, the decrease) between steady-state basal and steady-state stimulated effluent glucose concentrations. While somatostatin (1.4 .times. 10-7 M in the influent) had no effect on basal glucose release, it significantly inhibited (81%, P < 0.001) simultaneous glucagon (1.2 .times. 10-10 M)-induced hepatic glucose output, but not concurrent cAMP increments in the effluent. Somatostatin (1.4 .times. 10-8 M) also inhibited (38%, P < 0.05) glucagon (1.2 .times. 10-10 M)-induced glucose release. Inhibition by somatostatin (1.4 .times. 10-7 M) was overcome by a high concentration of glucagon (1.2 .times. 10-8 M) which was saturating for glucose but not cAMP production. In further experiments, somatostatin (1.4 .times. 10-7 M) blunted glucose mobilization by cAMP (1 .times. 10-3 M) infusion and suppressed theophylline (2.5 .times. 10-3 M)-potentiated, glucagon (6 .times. 10-11 M)-induced glucose output. It had no effect on glucose output stimulated by theophylline (2.5 .times. 10-3 M) alone and did not lower, over 6-10 min, glucose release into the effluent when added to a glucagon (1.2 .times. 10-10 M) infusion once steady-state glucose mobilization had been attained. Somatostatin directly suppresses glucagon-stimulated glucose release from rat liver in vitro in a dose-dependent manner, probably by a mechanism affecting cAMP action rather than its formation.