Influence of Epinephrine on Blood Sugar Utilization of Functionally Hepatectomized Rats.

Abstract

Previous experiments 1 have led to the conclusion that one of the principal causes for the epinephrine hyperglycemia consists in a decreased utilization of blood sugar in the tissues. It was pointed out that mobilization of liver glycogen alone is an inadequate explanation for the hyperglycemia, because there is not enough liver glycogen present to provide the tissues for hours with sugar at a rate which is greater than their normal ability to utilize sugar. Mobilization of liver glycogen can only lead to a protracted hyperglycemia of the type observed after epinephrine injections, (1) if a new formation of liver glycogen occurs which keeps pace with the conversion of liver glycogen into blood sugar and (2) if utilization of blood sugar itself is diminished. A new formation of liver glycogen exceeding its mobilization was demonstrated during epinephrine action and the source for the newly formed liver glycogen was found to be lactic acid derived from muscle glycogen. 1 That blood sugar utilization is low during epinephrine hyperglycemia was suggested by a comparison of the arterial and venous blood sugar concentration in men. Whereas the arteriovenous difference rises during alimentary hyperglycemia, it fails to do so during the much more pronounced epinephrine hyperglycemia, showing that the tissues are unable to withdraw sugar from the blood at a higher rate. A carbohydrate balance on sugar fed rats showed that the disposal of absorbed sugar after epinephrine injections is markedly diminished in the peripheral tissues. 1

Since epinephrine inhibits blood sugar utilization in the peripheral tissues of the intact animal, this should also be demonstrable on hepatectomized animals. Mann 2 found that epinephrine did not cause an increase in the blood sugar following hepatectomy or delay the development of the characteristic symptoms associated with hypoglycemia. This is not surprising, because muscle glycogen cannot contribute glucose directly to the blood; it can only do so indirectly through the intervention of the liver. In the absence of the liver, lactic acid derived from muscle glycogen can no longer be converted into glucose and consequently epinephrine is unable to produce hyperglycemia in hepatectomized animals. Since it takes several hours until the blood sugar falls to 50 mg. % in the hepatectomized dog and since the time at which hypoglycemic symptoms appear is variable, an inhibitory action of epinephrine on the fall in blood sugar might easily escape attention, or it might even be absent, owing to the extremely low utilization of blood sugar.