MEASUREMENTS OF ENDOGENOUS GLUCAGON IN PLASMA AND THE INFLUENCE OF BLOOD GLUCOSE CONCENTRATION UPON ITS SECRETION*

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Abstract
The development of a highly sensitive and specific radio-immunoassay for glucagon made possible these studies designed to identify circulating endogenous glucagon in plasma and to determine whether glucagon secretion is influenced by alteration in blood glucose concentration. Plasma obtained from the pancreaticoduodenal vein of 48 normal fasting dogs was found to contain a mean of 543 [mu][mu]g Eq per ml of glucagon, with a range of 0 to 1300 [mu][mu]g Eq per ml. In 9 dogs made chronically hypoglycemic by means of phlorizin administration, an average of 1976 [mu][mu]g Eq per ml was present, with a range of 680 to 3100 [mu][mu]g Eq per ml. Of 13 dogs made acutely hypoglycemic by means of administration of "glucagon-free" insulin, a gradual rise in glucagon concentration was noted in most, with significant elevations appearing during the second and third hours of severe hypoglycemia. In both the chronically and acutely hypoglycemic animals, the induction of intense hypoglycemia by means of the rapid intravenous injection of 25 g of glucose was followed by an abrupt suppression of hyperglucagonemia to baseline values; this suppression lasted until the glucose level returned toward normal, whereupon a brisk rise in glucagon concentration often appeared. These results provide the first specific identification of endogenous glucagon in plasma and demonstrate the influence of blood glucose concentration upon its secretion. They provide strong support for the view that glucagon is a hormone with a role in blood glucose regulation.