Blood Sugar Response to Intraperitoneal Epinephrine Injections in Normal and Hypophysectomized Dogs

Abstract

Aschner 1 showed that epinephrine subeutaneously administered produces less glycosuria in the hypophysectomized dog than in the normal. Other investigators 2 , 3 , 4 have since shown that epinephrine so administered produces less elevation of the blood sugar in hypophysectomized toads, rabbits and dogs than in the normal animals. Until the recent report of Russell and Cori 5 the impression therefore prevailed that the glycogenolytic action of epinephrine is diminished in hypophysectomized animals. These investigators demonstrated, however, that in the rat intravenously administered epinephrine produces an effect on blood sugar similar to that obtained in normal controls. In the course of certain investigations on the carbohydrate metabolism of hypophysectomized dogs observations were made by us on the effect of intraperitoneal injections of epinephrine on blood sugar which are herein reported.

Nine normal and 9 completely hypophysectomized dogs were injected intraperitoneally. In 3 animals observations were made under identical conditions before and after hypophysectomy. The dosage used was 0.75 cc. (1-1000) in 10 cc. of normal saline per 6 kg. of body weight. Coincidental studies on insulin sensitivity revealed that the hypophysectomized animals were 2 to 4 times as sensitive as the normals. Autopsy later established the completeness of the hypophysectomy. Some of the dogs studied were on a balanced diet of carbohydrate, fat and protein, others were on a high fat, low carbohydrate diet and a third group was on a low fat, high carbohydrate diet. The alterations in diet made no appreciable difference in the effectiveness of epinephrine as a glycogenolytic factor. The effect on blood sugar was determined by analyses made at frequent intervals, up to 6 hours, using the Shaffer and Somogyi sugar method. 6

Analysis of the results outlined in Tables I and II shows that epinephrine intraperitoneally administered is in general as effective in raising the blood sugar in hypophysectomized dogs as in the normal. Glycogen determinations on animals A.I and A.2, Table II, carried out in the post-absorptive state, showed 5.4% and 6.1% glycogen content for the liver and 0.75% and 1.06% for the muscle of the 2 animals. The method of analysis used was that of Good, Kramer and Somogyi. 7 It is apparent that hypophysectomized dogs, in a state of good nutrition, have an adequate liver and muscle glycogen supply to serve as substrate in the glycogenolytic process.

The reason for the lessened effect on blood sugar from subcutaneously administered epinephrine has not been definitely established. Russell and Cori suggested that it probably was due to a difference in the rate of absorption. Evidence in keeping with this explanation has been provided by one of us 8 in studies on the sensitivity of smooth musculature to exogenous epinephrine in cats as altered by hypophysectomy. It was found that the smooth musculature of such animals shows a definitely hyper dynamic contractibility (30-40%) on contact with epinephrine. This would result in an accentuated contraction of the blood vessels at the site of subcutaneous injection with a corresponding slowing of the rate of absorption. Such a factor would not be active on intravenous or on intraperitoneal injection where absorption would occur largely through the lymphatics.