Effect of Adrenal Steroids on Glucose Kinetics in Normal and Diabetic Dogs

The rates of endogenous glucose production, utilization, the amount of the intermixing glucose (“pool”) and the apparent distribution space were measured in conscious, trained normal and depancreatized dogs by the method of successive measured injections of tracer. During the intravenous infusion of hydrocortisone or methylprednisolone both the rates of glucose production and utilization fell in normal dogs. Since the same effect was obtained during the infusion of hydrocortisone in depancreatized dogs this effect of adrenal steroids does not seem to be due to an extra release of insulin. In normal dogs, daily injections of 4 mg. per kilogram of methylprednisolone for one week significantly increased the rates of glucose production and utilization and also the amount of intermixing glucose and the apparent glucose space, without any significant change in the concentration of glucose in the blood plasma. Prolongation of methylprednisolone treatment for a second week caused a further increase in all four parameters again with no change in plasma glucose level. The intravenous infusion of glucose was found to diminish the rate of endogenous glucose production to the same degree before as after one week of methylprednisolone treatment. In diabetic dogs deprived of insulin, two daily injections of methylprednisolone increased the rate of glucose production and the plasma concentration but not the apparent distribution space of glucose. These experiments indicate that in dogs the homeostasis of plasma glucose level is maintained in spite of markedly increased gluconeo genesis if pancreatic function is unimpaired.

[1]  A. Eisenstein,et al.  EFFECT OF ADRENAL STEROIDS ON CARBOHYDRATE METABOLISM IN VARIOUS ANIMAL SPECIES. , 1964, Endocrinology.

[2]  T. Hockaday Rapid Action of Hydrocortisone on the Increase in Blood Glucose after Adrenaline , 1964, Nature.

[3]  J. Jenkins,et al.  EFFECT OF ADRENOCORTICAL HORMONES ON RELEASE OF FREE FATTY ACIDS AND UPTAKE OF GLUCOSE IN HUMAN PERIPHERAL TISSUES. , 1964, Clinical science.

[4]  L. Madison,et al.  THE ACUTE EFFECT OF HYDROCORTISONE ON HEPATIC GLUCOSE OUTPUT AND PERIPHERAL GLUCOSE UTILIZATION. , 1964, The Journal of clinical investigation.

[5]  F. H. Tyler,et al.  EARLY EFFECT OF CORTISOL ON GLUCOSE METABOLISM IN MAN. , 1963, The Journal of laboratory and clinical medicine.

[6]  J. Ashmore,et al.  EFFECTS OF TRIAMCINOLONE ON CARBOHYDRATE SYNTHESIS BY RAT LIVER SLICES. , 1963, The Journal of biological chemistry.

[7]  A. Munck,et al.  Rapid Inhibition by Cortisol of Incorporation of Glucose in vivo into the Thymus of the Rat , 1962, Nature.

[8]  R. Haynes Studies of an vitro effect of glucocorticoids on gluconeogenesis. , 1962, Endocrinology.

[9]  J. Beck,et al.  Physiological importance of cortisol. , 1962, British medical bulletin.

[10]  A. Renold,et al.  Studies on rat adipose tissue in vitro. IX. Further effects cortisol on glucose metabolism. , 1962, The Journal of biological chemistry.

[11]  G. Hetényi,et al.  Rates of Production, Utilization, Accumulation and Apparent Distribution Space of Glucose: Effects of Insulin in Dogs Using a Validated Tracer Method , 1961, Diabetes.

[12]  B. Landau,et al.  Regulation of blood glucose concentration: response of liver to glucose administration. , 1961, The American journal of physiology.

[13]  B. Bowman,et al.  Hydrocortisone and some of its effects on intermediary metabolism. I. In vivo studies. , 1961, Endocrinology.

[14]  D. Steiner,et al.  Effects of Insulin, Glucagon, and Glucocorticoids upon Hepatic Glycogen Synthesis from Uridine Diphosphate Glucose , 1961 .

[15]  J. Willmer Changes in hepatic enzyme levels after adrenalectomy. I. Phosphorylase, phosphoglucomutase, and phosphoglucoseisomerase. , 1960, Canadian journal of biochemistry and physiology.

[16]  B. Overell,et al.  THE EFFECT OF HORMONES AND THEIR ANALOGUES UPON THE UPTAKE OF GLUCOSE BY MOUSE SKIN IN VITRO , 1960, The Journal of pharmacy and pharmacology.

[17]  C. E. Johnson,et al.  The effects of hydrocortisone on glycogen storage and phosphorylase activity of frog liver. , 1960, Journal of cellular and comparative physiology.

[18]  L. Leloir,et al.  Synthesis of glycogen from uridine diphosphate glucose in liver. , 1960, The Journal of biological chemistry.

[19]  J. Larner,et al.  INSULIN‐STIMULATED GLYCOGEN FORMATION IN RAT DIAPHRAGM * , 1959, Annals of the New York Academy of Sciences.

[20]  C. Park,et al.  REGULATION OF GLUCOSE UPTAKE IN HEART MUSCLE FROM NORMAL AND ALLOXAN‐DIABETIC RATS: THE EFFECTS OF INSULIN, GROWTH HORMONE, CORTISONE, AND ANOXIA * , 1959, Annals of the New York Academy of Sciences.

[21]  G. Hetényi,et al.  Successive measured injections of tracer as a method for determining characteristics of accumulation and turnover in higher animals with access limited to blood: tests in hydrodynamic systems and initial observations on insulin action in dogs. , 1959, Metabolism: clinical and experimental.

[22]  R. Steele Use of C14-glucose to measure hepatic glucose production following an intravenous glucose load or after injection of insulin. , 1959, Metabolism: clinical and experimental.

[23]  L. Leloir,et al.  Biosynthesis of glycogen from uridine diphosphate glucose. , 1959, Archives of biochemistry and biophysics.

[24]  F. Depocas Turnover of plasma glucose in anesthetized warm- and cold-acclimated rats exposed to cold. , 1959, Canadian journal of biochemistry and physiology.

[25]  P. Marks,et al.  Production of Glucose by the Liver during Hyperglycæmia , 1958, Nature.

[26]  N. Altszuler,et al.  Insulin hypersensitivity and physiological insulin antagonists. , 1958, Physiological reviews.

[27]  R. Steele,et al.  Effects of adrenocortical steroids on carbohydrate metabolism in hypophysectomized dogs; studies with C14-labeled glucose. , 1957, The American journal of physiology.

[28]  S. Fajans,et al.  The effect of adrenal steroids on blood levels of pyruvic and alpha-ketoglutaric acids in normal subjects. , 1957, Metabolism: clinical and experimental.

[29]  G. Beaton,et al.  Alanine-glutamic transaminase activity and protein metabolism. , 1957, Archives of biochemistry and biophysics.

[30]  M. Fabrykant,et al.  Cushing's syndrome: failure to demonstrate diminished peripheral glucose uptake and insulin resistance. , 1957, Metabolism: clinical and experimental.

[31]  D. Ingle Experimental Steroid Diabetes , 1956, Diabetes.

[32]  F. X. Hausberger,et al.  Over-all glucose utilization in steroid diabetic guinea pigs. , 1955, The American journal of physiology.

[33]  J. Jenkins,et al.  Acute effects of intravenous hydrocortisone on glucose and insulin tolerances, and levels of serum and urinary inorganic phosphorus. , 1955, The Journal of clinical endocrinology and metabolism.

[34]  D. Ingle,et al.  Effect of hydrocortisone on the level of plasma amino acids after removal of the intra-abdominal organs in the rat. , 1955, Metabolism: clinical and experimental.

[35]  D. Weakley,et al.  The influence of hormonal factors and of diet upon hepatic glucose-6-phosphatase activity. , 1955, The Journal of biological chemistry.

[36]  T. Frawley THE ROLE OF THE ADRENAL CORTEX IN GLUCOSE AND PYRUVIC ACID METABOLISM IN MAN INCLUDING THE USE OF INTRAVENOUS HYDROCORTISONE IN ACUTE HYPOGLYCEMIA , 1955, Annals of the New York Academy of Sciences.

[37]  J. Linsk,et al.  THE PARADOXICAL EFFECT OF INTRAVENOUS HYDROCORTISONE UPON CARBOHYDRATE METABOLISM , 1955, Annals of the New York Academy of Sciences.

[38]  K. Paschkis,et al.  Comparison of the diabetogenic action of cortisone and growth hormone in different species. , 1954, Endocrinology.

[39]  P. Bondy,et al.  Influence of adrenal cortical hormones upon the level of plasma amino acids in eviscerate rats. , 1954, Endocrinology.

[40]  R. E. Haist,et al.  Effect of ACTH and cortisone on the islets of Langerhans and the pancreas in intact and hypophysectomized rats. , 1954, The American journal of physiology.

[41]  M. Goldstein,et al.  Influence of the liver on uptake of glucose by extrahepatic tissues. , 1954, The American journal of physiology.

[42]  R. Boutwell,et al.  The acute effect of cortisone treatment on the utilization of glucose by the mouse. , 1954, Archives of biochemistry and biophysics.

[43]  M. Bacila,et al.  The effect of adrenal cortical hormones on the anaerobic glycolysis and hexokinase activity. , 1954, Endocrinology.

[44]  J. E. Nezamis,et al.  Effect of Adrenal Cortical Extract and Steroids upon Glucose Tolerance of Eviscerated Rats , 1953, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[45]  O. V. Sirek,et al.  Intramuscular Cortisone Administration to Dogs , 1952, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[46]  B. Katz,et al.  Utilization of carbohydrate by extrahepatic tissues of the adrenalectomized dog. , 1952, The American journal of physiology.

[47]  K. Lundbaek [Adrenal cortex and carbohydrate metabolism]. , 1952, Nordisk medicin.

[48]  A. N. Wick,et al.  THE DISPOSITION OF GLUCOSE BY THE EXTRAHEPATIC TISSUES , 1951, Annals of the New York Academy of Sciences.

[49]  H. Marques [Determination of the blood sugar]. , 1951, Revista de quimica e farmacia.

[50]  J. Kelleher,et al.  The effect of cortisone on normal sheep. , 1951, American journal of veterinary research.

[51]  J. Pincus,et al.  V. Effect of Epinephrine, AGTH and Cortisone on Citrate, Calcium, Glucose and Phosphate Levels in Rabbits.∗ , 1951, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[52]  D. Ingle,et al.  The biologic properties of cortisone: a review. , 1950, The Journal of clinical endocrinology and metabolism.

[53]  R. H. More,et al.  Diabetic State with Lipaemia and Hydropic Changes in the Pancreas Produced in Rabbits by Cortisone.∗ , 1950, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[54]  G. H. Keyes,et al.  Glycogenic effect of adrenal cortical extract. , 1949, The American journal of physiology.

[55]  G. R. Bartlett,et al.  The influence of insulin and adrenal cortical compounds on the metabolism of radioactive C14-glucose in the isolated rat diaphragm. , 1949, The Journal of biological chemistry.

[56]  C. Long A DISCUSSION OF THE MECHANISM OF ACTION OF ADRENAL CORTICAL HORMONES ON CARBOHYDRATE AND PROTEIN METABOLISM1,2 , 1942 .

[57]  G. W. Thorn,et al.  A COMPARISON OF THE EFFECTS OF 11-DESOXYCORTICOSTERONE ACETATE AND 17-HYDROXY-11-DEHYDRO-CORTICOSTERONE IN PARTIALLY DEPANCREATIZED RATS , 1941 .

[58]  J. Herrick,et al.  THE MECHANISM OF REGULATION OF THE BLOOD SUGAR BY THE LIVER , 1938 .

[59]  H. Silvette,et al.  EFFECTS OF CORTICO-ADRENAL EXTRACT ON CARBOHYDRATE METABOLISM IN NORMAL ANIMALS , 1932 .

[60]  N. Stamm,et al.  Regulation of enzymes involved in gluconeogenesis. , 1964, Advances in enzyme regulation.

[61]  D. Goldenberg,et al.  IN VITRO EFFECT OF ADRENAL STEROIDS ON CARBOHYDRATE SYNTHESIS IN LIVER. , 1964, Endocrinology.

[62]  G. Okuno Studies on the Delayed Increase of Liver Glycogen by Glucagon , 1960 .

[63]  S. Weinhouse,et al.  Turnover rates of blood glucose in normal dogs during hyperglycemia induced by glucose or glucagon. , 1958, The Journal of biological chemistry.

[64]  S. Fajans,et al.  Influence of adrenal cortical steroids on carbohydrate metabolism in man. , 1956, Metabolism: clinical and experimental.

[65]  R. W. McGilvery,et al.  The response to glucogenic stress of fructose-1, 6-diphosphatase in rabbit liver. , 1956, The Journal of biological chemistry.

[66]  F. X. Hausberger,et al.  Steroid diabetes in guinea pigs: effects of hydrocortisone administration on blood and urinary glucose, nitrogen excretion, fat deposition, and the islets of Langerhans. , 1955, Endocrinology.

[67]  G. Wrenshall Working basis for the tracer measurement of transfer rates of a metabolic factor in biological systems containing compartments whose contents do not intermix rapidly. , 1955, Canadian journal of biochemistry and physiology.

[68]  B. Houssay,et al.  Prevention of experimental diabetes with adrenal steroids. , 1954, Endocrinology.

[69]  W. W. Swingle,et al.  THE RÔLE OF THE ADRENAL CORTEX IN PHYSIOLOGICAL PROCESSES , 1944 .