Suppression of pancreatic
glucagon secretion by
hyperglycemia is a characteristic of normal alpha cell function. However, in diabetic subjects, plasma
glucagon is normal or high despite
hyperglycemia. It seemed possible that the presence of
glucose or its metabolites within the alpha cell might be essential for suppression of
glucagon secretion, and that in diabetes an intracellular deficiency of
glucose secondary to
insulin lack might be responsible for the nonsuppressibility. The present study was designed to determine the effect upon
glucagon secretion of blockade of
glucose metabolism and of experimental
insulin deficiency. Blockade of
glucose metabolism was induced in dogs by administration of
2-deoxyglucose or
mannoheptulose. A striking rise in
glucagon was observed despite accompanying
hyperglycemia and
hyperinsulinemia, which, in the case of
mannoheptulose, was induced by infusing crystalline
insulin. To determine if
insulin lack also causes paradoxical hyperglucagonemia, dogs were made severely diabetic by
alloxan. Fasting
glucagon levels ranged from 3 to 22 times normal despite severe
hyperglycemia, and were quickly restored to normal by infusing
insulin. Diabetes induced in rats by anti-
insulin serum was also associated with significant elevation in plasma
glucagon. However,
diazoxide-induced
insulin lack did not increase
glucagon in dogs. It is concluded that normal suppression of
glucagon secretion by
hyperglycemia does not occur when
glucose metabolism is blocked or when severe
insulin deficiency is produced. It is suggested that normal
glucose metabolism within the alpha cell may be an
insulin-requiring process without which hyperglycemic suppression of
glucagon release cannot occur.