[en] The mechanisms responsible for glucocorticoid-induced insulin resistance remain unclear. Glucocorticoids show several interactions with the sympatho-adrenal system which may contribute to this decrease in insulin sensitivity: they enhance the synthesis and actions of catecholamines, but abolish insulin-induced activation of muscle sympathetic nerve activity. The present study was performed in order to investigate the effects of the interactions between glucocorticoids and the sympatho-adrenal system on insulin sensitivity. Basal and insulin-stimulated glucose metabolism was measured in healthy human subjects during four 2-h clamp studies as follows: control (C); after taking oral dexamethasone (2 mg daily) for 2 days (D); after taking oral ephedrine sulphate (40 mg daily) for 2 days (E); and after taking dexamethasone+ephedrine (D+E). Glucose uptake, production and oxidation were calculated from plasma 13C glucose and exhaled 13CO2 during constant tracer infusion of U-13C glucose. Basal glucose production, utilization and oxidation were similar in all four studies. During hyperinsulinaemia, glucose uptake was reduced by 51.5% with treatment D, by 25.9% with treatment E, and by 49.6% with D+E. Glucose oxidation was reduced by 54.0% with treatment D, by 24.0% with treatment E, and by 57.2% with D+E. Hepatic glucose production was completely suppressed in all four studies. It is concluded that both dexamethasone and ephedrine decrease insulin-mediated glucose uptake and oxidation. Co-administration of ephedrine does not suppress the glucocorticoid-induced alterations of glucose metabolism. This indicates that glucocorticoid-induced insulin resistance is not related to the inhibition of muscle sympathetic nerve activity. These results suggest instead that glucocorticoids and sympathomimetic agents may impair glucose metabolism by common actions.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Paquot, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Schneiter, P.
Jequier, E.
Tappy, L.
Language :
English
Title :
Effects of glucocorticoids and sympathomimetic agents on basal and insulin-stimulated glucose metabolism.
Baron A.D., Wallace P., Brechtel G. (1987) In vivo regulation of non‐insulin‐mediated and insulin‐mediated glucose uptake by Cortisol. Diabetes 36:1230-1237.
Carter‐Su C., Okamoto K. (1985) Effect of glucocorticoids on hexose transport in rat adipocytes. J Biol Chem 260:11091-11098.
Cmasson J.‐L., Shiama H., Chu D.T.W. (1981) Inhibitory effect of epinephrine on insulin‐stimulated glucose uptake by rat skeletal muscle. J Clin Invest 68:706-713.
Cryer P.E. (1993) Catecholamines, pheochromocytoma, and diabetes. Diabetes Rev 1:309-317.
Davies A.O., Delean A., Lefkowitz R.J. (1981) Myocardial beta‐adrenergic receptors from adrenalec‐tomized rats: impaired formation of high‐affinity agonist‐receptor complexes. Endocrinology 108:720-722.
Debodo R., Steele R., Altszuler N., Dunn A., Bishop J. (1963) On the hormonal regulation of carbohydrate metabolism: studies with 14C‐glucose. Recent Prog Horm Res 19:445-488.
Defronzo R.A., Tobin J.D., Andres R. (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214.
Gay L.J., Schneiter P., Schutz Y., Di Vetta V., Jequier E., Tappy L. (1994) A non‐invasive assessment of hepatic glycogen kinetics and post‐absorptive gluconeogenesis in man. Diabetologia 37:517-523.
Harrison T.S., Chawla R., Wojtalik R.S. (1968) Steroidal influences on catecholamines. N Engl J Med 279:136-143.
Herbert V., Lau K.S., Gottlieb C.W., Bleicher S.J. (1965) Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab 25:1375-1384.
Jahoor F., Peters E.J., Wolfe R.R. (1990) The relationship between gluconeogenic substrate supply and glucose production in humans. Am J Physiol 258:E288.
Joost H.G., Weber T.M., Cushman S.W., Simpson I.A. (1986) Insulin‐stimulated glucose transport in rat adipose cells: modulation of transporter intrinsic activity by isoproterenol and adenosine. J Biol Chem. 261:10033-10036.
Kennedy B., Ziegler M.G. (1991) Cardiac epinephrine synthesis: regulation by a glucocorticoid. Circulation 84:891-899.
Kennedy B., Elayan H., Ziegler M.G. (1993) Glucocorticoid induction of epinephrine synthesizing enzyme in rat skeletal muscle and insulin resistance. J Clin Invest 92:303-307.
Laakso M., Edelman S.V., Brechtel G., Baron A.D. (1992) Effects of epinephrine on insulin‐mediated glucose uptake in whole body and legmuscle in humans: role of blood flow. Am J Physiol 263:E199.
Lembo G., Capaldo B., Rendina V., Iaccarino G., Napoli R., Guida R., Trimarco B., Sacca L. (1994) Acute noradrenergic activation induces insulin resistance in human skeletal muscle. Am J Phvsiol 266:E242.
Livesey G., Elia M. (1988) Estimation of energy expenditure, net carbohydrate utilization, and net fat oxidation and synthesis by indirect calorimetry evaluation of errors with special reference to the detailed composition of foods. Am J Clin Nutr 47:608-628.
Mcmahon M., Gerich J., Rizza R. (1988) Effects of glucocorticoids on carbohydrate metabolism. Diabetes/Metab Rev 4:17-30.
Malbon C.C., Hadcock J.H. (1988) Evidence that glucocorticoid response elements in the 5′ noncoding region of the hamster (32‐adrenergic receptor gene are obligate for glucocorticoid regulation of receptor mRNA levels. Biochem Biophvs Res Commun 154:676-681.
Nosadini R., Del Prato S., Tiengo A., Valerio A., Muggeo M., Opocher G., Mantero F., Duner E., Marescotti C., Mollo F., Belloni F. (1983) Insulin resistance in Cushing's syndrome. J Clin Endocrinol Metab 57:529-536.
Randle P., Garland P., Hales C., Newsholme E. (1963) The glucose fatty‐acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785-789.
Raz I., Katz A., Spencer M.K. (1991) Epinephrine inhibits insulin‐mediated glycogenesis but enhances glycolysis in human skeletal muscle. Am J Physiol 260:E430.
Rizza R.A., Cryer P.E., Haymond M.W., Gerich J.E. (1980) Adrenergic mechanisms for the effects of epinephrine on glucose production and clearance in man. J Clin Invest 65:682-689.
Robert J.J., Koziet J., Chauvet D., Darmaun D., Desjeux J.F., Young V.R. (1987) Use of 13C‐labeled glucose for estimating glucose oxidation: some design considerations. J Appl Physiol 6:1725-1732.
Scheidegger K., Robbins D.C., Danforth E. (1984) Effects of chronic beta receptor stimulation on glucose metabolism. Diabetes 3:1144-1149.
Scherrer U., Vollenweider P., Randin D., Jequier E., Nicod P., Tappy L. (1993) Suppression of insulin induced sympathetic activation and vasodilation by dexamethasone in humans. Circulation 88:388-394.
Tappy L., Acheson K., Normand S., Schneeberger D., THEalin A., Pachiaudi C., Riou J.P., JEaquier E. (1992) Effects of infused amino acids on glucose oxidation, endogenous glucose production and 13C glucose synthesis from 13C bicarbonate in healthy human subjects. Am J Physiol 262:E826.
Tappy L., Randin D., Vollenweider P., Vollenweider L., Paquot N., Scherrer U., PH., Nicod P., Jequier E. (1994) Mechanisms of dexamethasone‐induced insulin resistance in healthy humans. J Clin Endocrinol Metab 79:1063-1069.
Tappy L., Paquot N., Tounian P., PH., Jequier E. (1995) Assessment of glucose metabolism in humans with the simultaneous use of indirect calorimetry and tracer techniques. Clin Physiol 15:1-12.
Wolfe R.R. (1984) Specific applications: glucose metabolism. Tracers in Metabolic Research Radioisotope and Stable Isotope/Mass Spectrometry Methods , Wolfe, R. R., Alan R. Liss, New York; 112-129.
