Effect of insulin treatment upon response of extrapancreatic glucagon to arginine.

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Abstract
To investigate the effect of insulin treatment upon the secretion of extrapancreatic glucagon, Arg infusion was performed in normal dogs and alloxan diabetic dogs with or without insulin treatment at conscious and anesthetized states. In a series of experiments with conscious dogs, alloxan diabetic dogs revealed not only elevated fasting levels of plasma glucagon but also exaggerated glucagon response to Arg. Insulin treatment in the alloxan dogs reduced the fasting plasma glucagon levels as well as responsiveness of glucagon to Arg. In the experiments with anesthetized dogs, plasma glucagon in the portal vein of the normal dogs rose only sightly in response to Arg infused after total pancreatectomy. In contrast, the alloxan diabetic dogs revealed an increase in plasma glucagon following Arg infusion performed after pancreatectomy. The response of plasma glucagon to Arg was reduced after pancreatectomy in the alloxan diabetic dogs with insulin treatment. Total immunoreactive glucagon (IRG) measured by a non-specific antiserum, increased in response to Arg after pancreatectomy in both the normal and alloxan diabetic dogs. Insulin treatment reduced an exaggerated response of total IRG in alloxan diabetic dogs. Alloxan diabetic dogs have an increased response of plasma glucagon and extrapancreatic glucagon, which is reduced by insulin treatment. The difference in response of plasma glucagon to Arg in alloxan diabetic dogs and depancreatized dogs indicates that deficiency of insulin as well as pancreatic glucagon plays an important role in the secretion of extrapancreatic glucagon.