Epinephrine significantly inhibited glucose-induced insulin release in man, the threshold dose being about 20 ng./kg. per minute. Maximal effect was attained with 60 ng./kg. per minute. In the presence of the threshold epinephrine dose, the dose-response curve for glucose-induced insulin release seemed to be displaced almost in parallel to the right of the control, suggesting competitive Inhibition. With the high epinephrine dose the inhibition of insulin release was of a noncompetitive nature.

Epinephrine did not significantly suppress insulin release induced by either arginine or tolbutamide as compared with the effect of these insulinagogues when given at normoglycemia. Only in the case of glucagon did the high epinephrine dose (90 ng./kg. per minute) markedly inhibit the insulinogenic effect of the hormone (p<0.001) even when the effect of glucagon at normoglycemia was used as control.

Since glucose exerted synergistk effects on insulin release in-duced by the other insulinagogues (arginine, glucagon, and tolbutamide), the insulinogenic effect of these insulinagogues In the presence of epinephrine was compared with their effect under hyperglycemie conditions similar to those obtained with epinephrine alone. It was found that epinephrine at a dose of 30 ng./kg. per minute totally inhibited the synergism between the hyperglycemie and the insulinagogues on insulin release. The greater the synergism—as with arginine and glucagon—the larger was the percentage inhibition by epinephrine. A threefold increase in the epinephrine dose further reduced the insulin response.

Our experiments suggest that epinephrine—in the doses used—inhibited the effect of glucose on insulin release. This effect occurred regardless of whether glucose was used as the sole stimulator of insulin release or was used in synergism with such insulinagogues as arginine, tolbutamide, or glucagon.

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