Carbohydrate metabolism in rats with adrenocortical transplants
Richardson, Philip Morrison
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Many studies have been made of the part played the adrenal cortex in carbohydrate metabolism. The conclusions of these studies are chiefly based on the use of animals in the terminal stages of adrenal insufficiency, and are therefore subject to criticism. The use of the adrenalectomized rat with autoplastic adrenocortical tissue is considered to obviate some of these criticisms. A review of the literature of carbohydrate metabolism and the factors affecting it is given. The regulation of carbohydrate metabolism by the glands of internal secretion is discussed, with emphasis on the part played by the adrenal cortex. Adrenal cortical hormones possessing "cortin activity", and their assay, are reviewed, their comparative effects considered and summarized. A review of the studies made on carbohydrate metabolism in adrenalectomized rats is included. The problem of relative insufficiency of adrenocortical hormone is discussed and the literature reviewed. Studies of the rat with transplanted cortical tissue have shown that the transplanted tissue is able to maintain the life and health of the animal under ordinary conditions, but is not able to function as efficiently as does the normal gland under conditions of stress. The blood sugar in the rat with transplanted cortical tissue has been investigated but the literature contains no studies of the glycogen levels in such animals. EXPERIMENTAL PART. A mixed stock of male albino rats were bilaterally adrenalectomized (by the lumbar approach), followed by implantation of the removed glands (all in one operation) and a sufficient period of recovery (not less than six weeks). From these, one group of rats was subjected to a fasting period of 24 hours. Free access to water was allowed during the period. At the end of the fasting, period, the rats were anesthetized with sodium amytal (intraperitoneal injection - 10 mgms. per 100 gms. body weight). The abdominal cavity was opened and a sample of blood was obtained from the vena cava. The whole liver then was removed, weighed, and immediately placed in hot 30% potassium hydroxide solution. Samples of gastrocnemius muscle were obtained, weighed, and promptly placed in hot 30% potassium hydroxide. Determinations were made of the blood glucose (using the Somogyi-Shaffer-Hartman iodometric titration method), and of the glycogen of the liver and muscles (using Good, Kramer, and Somogyi's modification of Pflüger's method). A control group of intact animals was subjected to the same procedure. On other groups (including one group of completely adrenalectomized rats) a glucose meal was given at the end of the 24 hour fasting period. The procedure was as follows: At the end of the 24 hour fasting period, the rats were fed glucose solution (1.065 gms. glucose per 100 gms. body weight) by stomach tube without anesthesia or excitement. After an interval of one hour, one animal from each group wae anesthetized. Samples of blood and gastrocnemius muscle, and the whole livers were removed for glucose or glycogen analyses. The same procedure was carried out at the end of two, three, and so on, hours, up to seven hours, after the glucose meal. Determinations were made of the blood glucose, and the glycogen of the liver and muscles. RESULTS. At the end of the 24 hour fasting period, in seven normal male rats the blood glucose averaged 77 mgms. per 100 cc. whole blood (range, 66 - 93 mgms.); liver glycogen, 32 mgms. per 100 gms. wet liver (range, 8-83 mgms.); and muscle glycogen, 323 mgms. per 100 gms. wet muscle (range, 240 - 433 mgms.). Eleven male rats with adrenocortical transplants shoved the following picture after 24 hours of fasting: blood glucose averaged 80 mgms. per 100 cc. whole blood (range, 62-94 mgms.); liver glycogen 35 mgms. per 100 gms. wet liver (range, 4-91 mgms.); and muscle glycogen, 484 mgms. per 100 gms. wet muscle (range, 400 - 591 mgms.). These values are considered to be within the normal range, and in agreement with average values obtained by other investigators. It is concluded that the adrenalectomized rat with transplanted adrenal cortical tissue is like the normal rat after a 24 hour fasting period with respect to blood glucose, liver glycogen, and muscle glycogen. in the groups of animals given a glucose meal, the following results were obtained. The glucose tolerance curve of the rat with adrenocortical transplants was like that of the normal with respect to shape, but the curve was less sharp, and had slightly lower values than that of the normal intact animal. With respect to liver glycogen, the adrenalectomized animal failed to deposit any during a five hour period; the adrenalectomized rat with adrenocortical transplants did not store glycogen in the liver at a rate comparable to the intact animal, and in a seven hour period did not reach the levels attained by the normal animal. The adrenalectomized rat stored glycogen in the muscles, but not at the same rate as the normal or the 'transplant'. The normal rat and the rat with 'transplants' kept pace with each other in their ability to store glycogen in the muscles for the first four hours after the glucose meal, but at that point the storage mechanisms of the rat with 'transplants' appeared to have settled down to a steady rate, lower than that of the normal, while the rate at which the normal rat stored glycogen continued to increase. On the basis of these results, the glucose tolerance curve in the rat with 'transplants' is considered to be normal, and it is concluded that no gross differences in the rate of absorption exist in the 'transplant'. Explanations are considered for the leveling off of the curve of glycogen storage in the muscle of the 'transplant'. On the basis of previous evidence obtained on the adrenalectomized rat, it is suspected that increased utilization explains this difference between the 'transplant' and the normal, and that the animal with 'transplants' is deficient in the amount (or kind) of hormone produced by the regenerated cortical tissue which controls glycogen storage in the muscle. The impaired ability of the rat with 'transplants' to store glycogen in the liver at the same rate or to the sane extent as the normal is discussed. It is possible that in the 'transplant' there is a failure of the transplanted tissue to produce, to the same degree as the normal, the hormone which controls gluconeogenesis in the liver. It is suggested that an impairment of the carbohydrate metabolism may be related to the increased susceptibility of the 'transplant' to histamine and anaphylactic shock. It is also suggested that the hormones of the cortex may act synergistically with adrenaline on the organism in times of stress particularly. The intermediacy of the 'transplant' to the normal and the adrenalectomized rat with respect to carbohydrate metabolism is considered, and it ie observed that the evidence supports the theory that the adrenalectomized rat with transplanted cortical tissue does not function as efficiently as does the normal animal in acute emergencies. It is concluded that (a) the carbohydrate levels in the adrenalectomized rat with adrenocortical transplants are like those of the normal rat after a 24 hour period of fasting; (b) the rat with 'transplants' differs from the normal animal in those mechanisms responsible for the storage of glycogen in the tissues, being intermediate in this respect to the normal and the completely adrenalectornized rat, but more like the former; (c) possible explanations for this difference between the storage levels of the 'transplant' and the normal rat are that a relative cortical and/or medullary deficiency in the former leads to a decreased gluconeogenesis in the liver, and eventually increased utilization of carbohydrate in the muscle.
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