The effect of glucagon at various infusion rates on plasma levels of somatostatin-like immunoreactivity (SLI) was examined in conscious normal and chronic alloxan diabetic dogs. In normal dogs glucagon infused at 6, 36, and 120 ng/kg per min did not affect the peripheral venous plasma SLI levels. In diabetic dogs, however, peripheral venous plasma SLI levels in inferior vena cava rose significantly from a mean base-line value of 181 ± 9 pg/ml to a peak value of 279 ± 38 pg/ml during the infusion of 120 μg/kg per min of glucagon, which raised plasma immunoreactive glucagon to > 5,000 pg/ml. This glucagon-mediated increase was completely abolished by coinfusion of 7 mU/kg per min of insulin, a rate that maintained the ratio of insulin to glucagon at approximately the baseline value. In anesthetized normal dogs the concentration of SLI in the venous effluent of the pancreas, the gastric fundus and the antrum increased significantly with each infusion rate of glucagon using including the lowest rate of 4 ng/kg per min, which raised the plasma level of glucagon to 395 ± 19 pg/ml. This stimulatory effect on SLI secretion was completely abolished by insulin coinfusion at a rate designed to maintain the insulin to glucagon ratio at approximately the baseline value, but the effect of a high 90-ng/kg per min infusion on pancreatic and gastric SLI release was not suppressed by coinfusion of 10 mU/kg per min insulin. These results suggest that glucagon stimulates splanchnic D cells unless insulin secretion is proportionally stimulated and suggests that the splanchnic D cell is a common target upon which the two hormones exert opposing actions. The loss of insulin inhibition of glucagon-mediated somatostatin secretion may account for the hypersomatostatinemia of severe diabetes.
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