Effects of Starvation on Plasma Pancreatic Glucagon in Normal Man

Abstract

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.

Plasma Growth Hormone, Insulin, and Glucagon Responses to Arginine Infusion in Children and Adolescents with Idiopathic Short Stature, Isolated Growth Hormone Deficiency, Panhypopituitarism, and Anorexia Nervosa

“…Indeed, the poorest plasma I R I responses to arginine were observed in the groups (i.e., anorexia nervosa, panhypopituitarism, and isolated growth hormone deficiency) which has blood glucose concentrations (fasting and postarginine infusion) lower than normal; however, the individual differences do not appear to be explained on this basis. Hypoinsulinemia has also been reported in chronic starvation (I I, 17, 23) and prolonged fasting has been reported to blunt the insulin secretory response to arginine (2). Similarly, in the present study, the mean plasma IRI response to arginine in the six adolescent females with anorexia nervosa was significantly less than in the normal group.…”

Leptin increases circulating glucose, insulin and glucagon via sympathetic neural activation in fasted mice

“…35 The observed reduction of plasma glucagon after 24 h fasting is, however, at variance with a previous study in which we observed a 22% increase in plasma glucagon after overnight fasting in mice in conjunction with similar level of glycaemia as in the present study. 42 The glucagon response to fasting is not well understood because both increased, 43 decreased 44,45 and unaffected 46 levels have been reported in humans. Whether these discrepancies in glucagon responses to energy restriction result from different lengths of fasting, different antibodies for the determination of glucagon (some antibodies cross react with immunoglobulins, 47 ) or other conditions, deserves to be studied in more detail.…”

Natriuresis of Fasting in Intact and Adrenalectomized Rats

“…It has been reported that glucagon en hanced the urinary excretion of sodium and water (12)(13)(14), and when we infused glucagon into the renal artery in non-fasted rats a similar effect was noted (unpublished data). It was also reported that the plasma concentration of glucagon increased early in the fast (14,29,30). These findings suggest that glucagon may play an important role in fasting-induced natriuresis.…”