To document and characterize the immediate phase of glucagon secretion as detected in peripheral blood in man, we have given pulses of L-arginine (0.1 gm. to 10.0 gm.) intravenously over twenty to thirty seconds to twenty-three healthy young men. Peak glucagon and insulin levels averaging four and five times basal levels respectively were reached two to five minutes after arginine administration and had returned to baseline levels by fifteen to thirty minutes. Computing the area above basal for the initial ten minutes after arginine stimulation established a dose-response relationship for the acute phases of glucagon and insulin secretion. A maximal glucagon response was elicited by doses of arginine of 5.0 gm. or greater, whereas for insulin, the plateau was reached at 2.5 gm. of arginine. Sequential 5.0-gm. pulses of arginine administered every thirty minutes showed that there was no augmentation or attenuation of the timing, magnitude (area 0-10 minutes) or absolute peak values reached for either the glucagon or insulin responses. The effect of induced hyperglycemia on the acute phase of insulin and glucagon secretion was assessed by administering the arginine during marked elevation of ambient glucose concentration achieved by the intravenous administration of glucose. This resulted in marked suppression of the acute glucagon response and dramatic accentuation of the insulin response.

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