Dose-dependent inhibitory and non-inhibitory action of somatostatin on insulin release in rats

The dose-dependent effect of intravenously infused synthetic somatostatin-14 on basal and postprandial insulin and gastrin release was assessed in anesthetized rats. Infusion of 1 ng · kg^-1 · min^-1 elicited a significant reduction of basal and postprandial insulin levels compared to the saline control group. At 15 ng · kg^-1 · min^-1 basal insulin was not affected but postprandial insulin levels were still significantly reduced. At 30 ng · kg^-1 · min^-1 neither basal nor stimulated insulin levels were affected. At the highest concentration of 120 ng · kg^-1 · min^-1 basal and postprandial insulin levels were suppressed similar to the lowest infusion rate of 1 ng · kg^-1 · min^-1. Basal gastrin levels were significantly reduced only at the highest rate of 120 ng · kg^-1 · min^-1. A significant reduction of postprandial gastrin levels was observed at 15 ng · kg^-1 · min^-1 and all higher infusion rates employed. Measurements of plasma somatostatin-like immunoreactivity (SLI) demonstrated that plasma SLI levels during the lowest infusion rate of 1 ng · kg^-1 · min^-1 were not different from the controls. No significant rise of plasma SLI levels was observed in response to the test meal. The higher infusion rates elicited a dose-dependent increase in plasma SLI levels. These data demonstrate that in rats somatostatin exerts a biological effect on insulin release at very low doses while certain greater infusion rates have no suppressive effect. Gastrin secretion is inhibited in a more linear pattern.