Epinephrine Liberation during Insulin Hypoglycaemia

Abstract

Insulin-Lilly was given intravenously in doses varying from 0.25 to 10 units per kilo of body weight to dogs, from which the suprarenal vein blood, and the ear vein blood (for the blood sugar) were collected and the mean arterial blood pressure from the femoral artery was recorded without fastening, narcotizing or evoking pain at all. Epinephrine was estimated by means of the rabbit intestine segment method.
(1) In all the cases the epinephrine output rate was increased, thirty minutes after the administration a definite acceleration was invariably noted, and when the dose was sufficiently large as 3 units per kilo or more, the hyperepinephrinaemia lasted for about two hours or longer. About ten to twenty times the initial rate was the usual outcome; with a small dosage as 0.25 units per kilo the acceleration was small as 3 times the initial and with a large dose as 10 units per kilo it was remarkable as about fifty times the initial. The maximum rate arrived at was from 0.0001 mgrm. to 0.0007 mgrm. per kilo per minute. When the blood sugar content went down to 0.06 or less, the acceleration became definite. In five out of 7 instances the hyperepinephrinaemia and the hypoglycaemia set in and progressed nearly simultaneously, but in the others, two cases, the hypoglycaemia started clearly before the hyperepinephrinaemia by about 15 minutes. And the epinephrine output velocity tended to recover the initial rate when the blood sugar concentration was still low or very low. In two cases the liberation rate and the blood sugar concentration recovered the initial values with wholly the same step, and in these both figures showed nearly completely the mirror image figures with each other.
With small dosages which were not sufficient to elicit any visible disturbances in the behaviour of animals the epinephrine discharge was thus augmented. But it must be added that in these cases there were noted definite changes in all the measurements, the blood sugar blood pressure, respiration, pulse rate and the body temperature.
(2) The mean arterial blood pressure usually fell on administering insulin, with or without a preliminary small elevation, but in a few instances only an elevation was brought about, which occurred and progressed in parallel with the epinephrine discharge rate. The blood pressure recovered from the fall earlier than that of the blood sugar concentration.
(3) The body temperature increased on insulin intoxication, though not so excessively, and the variation went hand in hand with that in the epinephrine liberation. The respiration frequency increased also in the later stage of intoxication, and when a violent acceleration occurred in the respiration rate, the blood sugar concentration was very low but the epinephrine output rate was already on the declination period. It may be noted by way of precaution that a very low concentration of the blood sugar was not invariably accompanied by a highly exaggerated rate of breathing.