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.

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