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부신피질 홀몬과 당, 단백 및 지질대사

CARBOHYDRATE PROTEIN AND LIPID METABOLISM OF THE GLUCOCORTICOIDS

한국의과학 1970년 2권 2호 p.29 ~ 32
이상종,
소속 상세정보
이상종 (  ) - 고려병원 내과

Abstract


Corticosterone has a definite, albeit weak, anti-anabolic and catabolic effect whereby protein is. converted into carbohydrate and fat. Since in abundance it is only one-fifth to one-tenth of cortisol in the adrenal effluent, it appears to have little importance in man.
Cortsol and cortisone are the most important glucocorticoids in man. A marked enhancement of gluconeogenesis is their prime metabolic effect. Long, Katzin, and Fry first established this point in 1940 by showing very large increase in liver glycogen and a marked nitrogen loss in balance studies on mice.
Stetten and Ingle were able to show by the use of radioactive labeling techniques that, in the mouse, corticoid induced hyperglycemia and glycosuria are very largely due to increased gluconeogenesis and only to a very small extent to peripheral antagonism to insulin in conjunction with growth hormone. A rise in blood sugar is temporarily opposed by increased secretion of insulin, which in turn tends to enhance fat synthesis, but eventually diabetes may follow. Steroid diabetes is seldom accompanied by ketoacidosis. A permissive action of cortisol is again evident, in that epinephrine and glucogen require the presence of cortisol in order to release significant amounts of glucose from liver glycogen.
In adrenal failure and after adrenalectomy, fasting or the ingestion of carbohydrate-poor diet leads to hypoglycemia. This is corrected by the administration of glucocorticoids. At the same time there is a raised excretion of nitrogen. The administration of pharmacological doses of glucocorticoid leads to hyperglycemia, glycosuria, diabetic reaction to the admiristration of glucose and increased deposition of glucose in the liver. An increase in the blood sugar concentration may be due to an increased glucose production in the liver or a reduction in the utilization of glucose. The ability of glucocorticoids to increase gluconeogenesis is well documented.
It would appear that the increased glucose production is due in part to the fact that the glucocorticoids have an inhibitory effect on the conversion of pyruvic acid to acetyl-coenzyme A. This leads to an accumlation of pyruvic acid, which again leads to the resynthesis of glucose. The glucocorticoids would seem to have no effect on the utilization of glucose when they are administered in
physiological doses. After large doses, there is in contrast a reduction in utilization. It has not been clarified whether this is due to the steroid itself, or whether it is due to a relative lack of insulin.
The increased deposition of glycogen in th liver is observed three to twenty-four hours after the
administration of glucocorticoids; this is considerably later than the increase in blood sugar concentration. On the other hand, it shows a close correlation with the increased excretion of nitrogen in urine.
The catabolic or anti-anabolic effect of the glucocorticoids is best demonstrated by patients who either produce too much hydrocortisone or who have received excessive amounts of glucocorticoids. The negative nitrogen balance is associated with inhibition of growth, osteoporosis, muscular atrophy, reductin in skin thickness and in the amount of lymphoid tissue. On the other hand, the protein -content of the liver increases. The catabolic action of the glucocorticoids may be a result od the .demonstrated increase in the uptake and breakdown of amino acids in the liver.
A large part of the amino acids is deaminated and converted to glucose, but part of them is also utilized for the synthesis of protein, especially ribonucleic acids and enzymes. The amounts in the liver of a numder of the enzymes which are involved in the carbohydrate and protein metabolism increase during glucocorticoid therapy. With a few exceptions the increases are secondary to the changes in carbohydrate and protein metabolism which have been mentioned. In this connection, it should be ,brought to mind that the metabolic changes caused by the glucocorticoids are counteracted by insulin. Adrenalectomy leads to improvement in an existing diabetes mellitus, and steroid-diabetes is a wellrecognized phenomenon. The glucocorticoids increase the peripheral breakdown of proteins. In the liver the glucocorticoids enhance the synthesis of enzyme protein, whilst this process is inhibited by insulin.
The effects of cortisol on fat metabolism are quite definite at the physiologic level. It induces a contripetal redistribution of fat, meantime increasing the total amount at the expense of protein. Earlier experiment (Kendall) in rodents revealed that, whereas cortisol led to protein depletion and diabetes primarily, corticosterone favored the deposition of fat under the experimental conditions -employed. Chronic excess of cortisol leads to hyperlipemia and hypercholesterolemia. At the cellular _level the mechanisms involved are multiple but deamination of amino acids is markedly increased by enhancing the activity of key enzymes involved in deamination and transamination through enzyme induction requiring a period of hours for maximal activity.

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