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Recent questions concerning the role of glucagon as a hormone of “glucose need” prompted this evaluation of glucose-glucagon relationships. To obviate certain problems relating to the sensitivity and specificity of the glucagon radioimmunoassay of peripheral venous plasma, glucagon was assayed in pancreatic venous effluent plasma obtained from conscious dogs with indwelling catheters in the pancreaticoduodenal vein. The effect of change in glucose concentration upon the pancreaticoduodenal vein glucagon concentration was determined. Insulin induced hypoglycemia was uniformly associated with a rise in pancreaticoduodenal vein glucagon concentration to a peak of 5.7 mμg./ml. at thirty minutes. The hyperglucagonemia continued intermittently during the hypoglycemic period but fell promptly during hyperglycemia induced by rapid injection of glucose. Hyperglycemia, induced in fifteen dogs by glucose infusion, was accompanied by a decline of glucagon from 2.7 to 1.8 mμg./ml. Cataglycemia, induced by rapid termination of a glucose infusion, produced a rise of glucagon in three of six dogs. Stimulation of glucagon secretion by hyperaminoacidemia was blocked by hyperglycemia induced by glucose infusion. The effect of starvation upon twenty-four-hour secretion of glucagon could not be determined in these studies. Wide variations in pancreaticoduodenal vein glucagon concentration made meaningful comparison of day-to-day changes impossible. A statistically significant negative correlation was observed between rapidly induced change in plasma glucose concentration and change in pancreaticoduodenal vein glucagon levels. The findings are compatible with the view that glucagon is a hormone of glucose need, which probably functions in the moment-to-moment regulation of blood glucose homeostasis and the maintenance of the so-called “normal” blood glucose limits.

The role of pancreatic glucagon in starvation has been difficult to assess in humans because of the nonspecificity of antisera heretofore available for glucagon radioimmunoassay. The development of a relatively specific antispnim for pacreation glucagon has now made possible valid measurements of pancreatic glueagun in human plasma and the effect of total starvation on plasma glucagon was, therefore, re-examined. Ten healthy male volunteers abstained from food for seventy-two hours or longer. During this period the mean level of glucose declined from 86 to 70 mg./100 ml., insulin declined from 10 to 3 μ./ml., while glucagon rose progressively from a mean prestarvation level of 126 μμg./ml. to 157, 189, and 178 μμg./ml. at the end of one, two, and three days' starvation, respectively. The responsiveness of the alpha cells to arginine stimulation was tested at the end of the starvation period by means of a forty-minute infusion of arginine at a rate of 11.5 mg./kg./min. Every one of the five subjects tested exhibited a prompt rise in glucagon secretion which reached a peak of 516 μμg./ml. in thirty minutes, significantly greater than the glucagon response of fed controls. Mean insulin concentration during the arginine infusion rose only 6.8 μU./ml. in contrast to a 29 μU./ml. rise in fed subjects. The biologic effect of the modest rise (about 50 per cent) in glucagon concentration would be exaggerated by the concomitant decline in insulin concentration. The magnitude and promptness of the gjucagon response to arginine suggests that the pancreas contains abundant glucagon after three days of total starvation.