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Published in: Diabetologia 2/2005

01-02-2005 | Article

Dexamethasone impairs muscle energetics, studied by 31P NMR, in rats

Authors: J.-F. Dumas, G. Bielicki, J.-P. Renou, D. Roussel, P.-H. Ducluzeau, Y. Malthièry, G. Simard, P. Ritz

Published in: Diabetologia | Issue 2/2005

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Abstract

Aims/hypothesis

Glucocorticoid treatments are associated with increased whole-body oxygen consumption. We hypothesised that an impairment of muscle energy metabolism can participate in this increased energy expenditure.

Methods

To investigate this possibility, we have studied muscle energetics of dexamethasone-treated rats (1.5 mg kg−1 day−1 for 6 days), in vivo by 31P NMR spectroscopy. Results were compared with control and pair-fed (PF) rats before and after overnight fasting.

Results

Dexamethasone treatment resulted in decreased phosphocreatine (PCr) concentration and PCr:ATP ratio, increased ADP concentration and higher PCr to γ-ATP flux but no change in β-ATP to β-ADP flux in gastrocnemius muscle. Neither 4 days of food restriction (PF rats) nor 24 h fasting affected high-energy phosphate metabolism. In dexamethasone-treated rats, there was an increase in plasma insulin and non-esterified fatty acid concentration.

Conclusions/interpretation

We conclude that dexamethasone treatment altered resting in vivo skeletal muscle energy metabolism, by decreasing oxidative phosphorylation, producing ATP at the expense of PCr.
Literature
1.
go back to reference Stanley WC, Lopaschuk GD, McCormack JG (1997) Regulation of energy substrate metabolism in the diabetic heart. Cardiovasc Res 34:25–33CrossRef Stanley WC, Lopaschuk GD, McCormack JG (1997) Regulation of energy substrate metabolism in the diabetic heart. Cardiovasc Res 34:25–33CrossRef
2.
go back to reference Scheuermann-Freestone M, Madsen PL, Manners D et al (2003) Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes. Circulation 107:3040–3046CrossRef Scheuermann-Freestone M, Madsen PL, Manners D et al (2003) Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes. Circulation 107:3040–3046CrossRef
3.
go back to reference Stump CS, Short KR, Bigelow ML, Schimke JM, Nair KS (2003) Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts. Proc Natl Acad Sci USA 100:7996–8001CrossRef Stump CS, Short KR, Bigelow ML, Schimke JM, Nair KS (2003) Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts. Proc Natl Acad Sci USA 100:7996–8001CrossRef
4.
go back to reference Perez-Carreras M, Del Hoyo P, Martin MA et al (2003) Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis. Hepatology 38:999–1007CrossRef Perez-Carreras M, Del Hoyo P, Martin MA et al (2003) Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis. Hepatology 38:999–1007CrossRef
5.
go back to reference Petersen KF, Befroy D, Dufour S et al (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300:1140–1142CrossRef Petersen KF, Befroy D, Dufour S et al (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300:1140–1142CrossRef
6.
go back to reference Rizza RA, Mandarino LJ, Gerich JE (1982) Cortisol-induced insulin resistance in man: impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action. J Clin Endocrinol Metab 54:131–138PubMed Rizza RA, Mandarino LJ, Gerich JE (1982) Cortisol-induced insulin resistance in man: impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action. J Clin Endocrinol Metab 54:131–138PubMed
7.
go back to reference Willi SM, Kennedy A, Wallace P, Ganaway E, Rogers NL, Garvey WT (2002) Troglitazone antagonizes metabolic effects of glucocorticoids in humans: effects on glucose tolerance, insulin sensitivity, suppression of free fatty acids, and leptin. Diabetes 51:2895–2902 Willi SM, Kennedy A, Wallace P, Ganaway E, Rogers NL, Garvey WT (2002) Troglitazone antagonizes metabolic effects of glucocorticoids in humans: effects on glucose tolerance, insulin sensitivity, suppression of free fatty acids, and leptin. Diabetes 51:2895–2902
8.
go back to reference Guillaume-Gentil C, Assimacopoulos-Jeannet F, Jeanrenaud B (1993) Involvement of non-esterified fatty acid oxidation in glucocorticoid-induced peripheral insulin resistance in vivo in rats. Diabetologia 36:899–906 Guillaume-Gentil C, Assimacopoulos-Jeannet F, Jeanrenaud B (1993) Involvement of non-esterified fatty acid oxidation in glucocorticoid-induced peripheral insulin resistance in vivo in rats. Diabetologia 36:899–906
9.
go back to reference Woodward CJ, Emery PW (1989) Energy balance in rats given chronic hormone treatment. 2. Effects of corticosterone. Br J Nutr 61:445–452 Woodward CJ, Emery PW (1989) Energy balance in rats given chronic hormone treatment. 2. Effects of corticosterone. Br J Nutr 61:445–452
10.
go back to reference Tataranni PA, Larson DE, Snitker S, Young JB, Flatt JP, Ravussin E (1996) Effects of glucocorticoids on energy metabolism and food intake in humans. Am J Physiol 271:E317–E325 Tataranni PA, Larson DE, Snitker S, Young JB, Flatt JP, Ravussin E (1996) Effects of glucocorticoids on energy metabolism and food intake in humans. Am J Physiol 271:E317–E325
11.
go back to reference Brillon DJ, Zheng B, Campbell RG, Matthews DE (1995) Effect of cortisol on energy expenditure and amino acid metabolism in humans. Am J Physiol 268:E501–E513 Brillon DJ, Zheng B, Campbell RG, Matthews DE (1995) Effect of cortisol on energy expenditure and amino acid metabolism in humans. Am J Physiol 268:E501–E513
12.
go back to reference Dumas JF, Simard G, Roussel D, Douay O, Foussard F, Malthiery Y, Ritz P (2003) Mitochondrial energy metabolism in a model of undernutrition induced by dexamethasone. Br J Nutr 90:969–977CrossRef Dumas JF, Simard G, Roussel D, Douay O, Foussard F, Malthiery Y, Ritz P (2003) Mitochondrial energy metabolism in a model of undernutrition induced by dexamethasone. Br J Nutr 90:969–977CrossRef
13.
go back to reference Roussel D, Dumas JF, Augeraud A et al (2003) Dexamethasone treatment specifically increases the basal proton conductance of rat liver mitochondria. FEBS Lett 541:75–79CrossRef Roussel D, Dumas JF, Augeraud A et al (2003) Dexamethasone treatment specifically increases the basal proton conductance of rat liver mitochondria. FEBS Lett 541:75–79CrossRef
14.
go back to reference Pignatelli D, Magalhaes MM, Magalhaes MC (1998) Direct effects of stress on adrenocortical function. Horm Metab Res 30:464–474 Pignatelli D, Magalhaes MM, Magalhaes MC (1998) Direct effects of stress on adrenocortical function. Horm Metab Res 30:464–474
15.
go back to reference Mitsuo T, Rounds J, Prechek D, Wilmore DW, Jacobs DO (1996) Glucocorticoid receptor antagonism by mifepristone alters phosphocreatine breakdown during sepsis. Arch Surg 131:1179–1185 Mitsuo T, Rounds J, Prechek D, Wilmore DW, Jacobs DO (1996) Glucocorticoid receptor antagonism by mifepristone alters phosphocreatine breakdown during sepsis. Arch Surg 131:1179–1185
16.
go back to reference Minet-Quinard R, Moinard C, Walrand S et al (2000) Induction of a catabolic state in rats by dexamethasone: dose or time dependency? JPEN J Parenter Enteral Nutr 24:30–36PubMed Minet-Quinard R, Moinard C, Walrand S et al (2000) Induction of a catabolic state in rats by dexamethasone: dose or time dependency? JPEN J Parenter Enteral Nutr 24:30–36PubMed
17.
go back to reference Caldefie-Chezet F, Moinard C, Minet-Quinard R, Gachon F, Cynober L, Vasson M (2001) Dexamethasone treatment induces long-lasting hyperleptinemia and anorexia in old rats. Metabolism 50:1054–1058CrossRef Caldefie-Chezet F, Moinard C, Minet-Quinard R, Gachon F, Cynober L, Vasson M (2001) Dexamethasone treatment induces long-lasting hyperleptinemia and anorexia in old rats. Metabolism 50:1054–1058CrossRef
18.
go back to reference Alger JR, Shulman RG (1984) NMR studies of enzymatic rates in vitro and in vivo by magnetization transfer. Q Rev Biophys 17:83–124 Alger JR, Shulman RG (1984) NMR studies of enzymatic rates in vitro and in vivo by magnetization transfer. Q Rev Biophys 17:83–124
19.
go back to reference Ravalec X, Le Tallec N, Carre F, de Certaines JD, Le Rumeur E (1996) Improvement of muscular oxidative capacity by training is associated with slight acidosis and ATP depletion in exercising muscles. Muscle Nerve 19:355–361 Ravalec X, Le Tallec N, Carre F, de Certaines JD, Le Rumeur E (1996) Improvement of muscular oxidative capacity by training is associated with slight acidosis and ATP depletion in exercising muscles. Muscle Nerve 19:355–361
20.
go back to reference Unitt JF, Schrader J, Brunotte F, Radda GK, Seymour AM (1992) Determination of free creatine and phosphocreatine concentrations in the isolated perfused rat heart by 1H- and 31P-NMR. Biochim Biophys Acta 1133:115–120CrossRef Unitt JF, Schrader J, Brunotte F, Radda GK, Seymour AM (1992) Determination of free creatine and phosphocreatine concentrations in the isolated perfused rat heart by 1H- and 31P-NMR. Biochim Biophys Acta 1133:115–120CrossRef
21.
go back to reference Heerschap A, Houtman C, in’t Zandt HJ, van den Bergh AJ, Wieringa B (1999) Introduction to in vivo 31P magnetic resonance spectroscopy of (human) skeletal muscle. Proc Nutr Soc 58:861–870 Heerschap A, Houtman C, in’t Zandt HJ, van den Bergh AJ, Wieringa B (1999) Introduction to in vivo 31P magnetic resonance spectroscopy of (human) skeletal muscle. Proc Nutr Soc 58:861–870
22.
go back to reference Lawson JW, Veech RL (1979) Effects of pH and free Mg2+ on the Keq of the creatine kinase reaction and other phosphate hydrolyses and phosphate transfer reactions. J Biol Chem 254:6528–6537 Lawson JW, Veech RL (1979) Effects of pH and free Mg2+ on the Keq of the creatine kinase reaction and other phosphate hydrolyses and phosphate transfer reactions. J Biol Chem 254:6528–6537
23.
go back to reference Gadian DG (1995) NMR and its applications to living systems, 2nd edn. Oxford Science Publications, Oxford Gadian DG (1995) NMR and its applications to living systems, 2nd edn. Oxford Science Publications, Oxford
24.
go back to reference Bittl JA, DeLayre J, Ingwall JS (1987) Rate equation for creatine kinase predicts the in vivo reaction velocity: 31P NMR surface coil studies in brain, heart, and skeletal muscle of the living rat. Biochemistry 26:6083–6090 Bittl JA, DeLayre J, Ingwall JS (1987) Rate equation for creatine kinase predicts the in vivo reaction velocity: 31P NMR surface coil studies in brain, heart, and skeletal muscle of the living rat. Biochemistry 26:6083–6090
25.
go back to reference Dobbins RL, Malloy CR (2003) Measuring in-vivo metabolism using nuclear magnetic resonance. Curr Opin Clin Nutr Metab Care 6:501–509 Dobbins RL, Malloy CR (2003) Measuring in-vivo metabolism using nuclear magnetic resonance. Curr Opin Clin Nutr Metab Care 6:501–509
26.
go back to reference Dawson MJ, Gadian DG, Wilkie DR (1980) Mechanical relaxation rate and metabolism studied in fatiguing muscle by phosphorus nuclear magnetic resonance. J Physiol 299:465–484 Dawson MJ, Gadian DG, Wilkie DR (1980) Mechanical relaxation rate and metabolism studied in fatiguing muscle by phosphorus nuclear magnetic resonance. J Physiol 299:465–484
27.
go back to reference Kushmerick MJ, Moerland TS, Wiseman RW (1992) Mammalian skeletal muscle fibers distinguished by contents of phosphocreatine, ATP, and Pi. Proc Natl Acad Sci USA 89:7521–7525 Kushmerick MJ, Moerland TS, Wiseman RW (1992) Mammalian skeletal muscle fibers distinguished by contents of phosphocreatine, ATP, and Pi. Proc Natl Acad Sci USA 89:7521–7525
28.
go back to reference Gardiner PF, Montanaro G, Simpson DR, Edgerton VR (1980) Effects of glucocorticoid treatment and food restriction on rat hindlimb muscles. Am J Physiol 238:E124–E130 Gardiner PF, Montanaro G, Simpson DR, Edgerton VR (1980) Effects of glucocorticoid treatment and food restriction on rat hindlimb muscles. Am J Physiol 238:E124–E130
29.
go back to reference Lewis MI, Monn SA, Sieck GC (1992) Effect of corticosteroids on diaphragm fatigue, SDH activity, and muscle fiber size. J Appl Physiol 72:293–301 Lewis MI, Monn SA, Sieck GC (1992) Effect of corticosteroids on diaphragm fatigue, SDH activity, and muscle fiber size. J Appl Physiol 72:293–301
30.
go back to reference Prezant DJ, Karwa ML, Richner B, Maggiore D, Gentry EI, Cahill J (1997) Gender-specific effects of dexamethasone treatment on rat diaphragm structure and function. J Appl Physiol 82:125–133 Prezant DJ, Karwa ML, Richner B, Maggiore D, Gentry EI, Cahill J (1997) Gender-specific effects of dexamethasone treatment on rat diaphragm structure and function. J Appl Physiol 82:125–133
31.
go back to reference Prezant DJ, Karwa ML, Richner B et al (1998) Short-term vs. long-term dexamethasone treatment: effects on rat diaphragm structure and function. Lung 176:267–280 Prezant DJ, Karwa ML, Richner B et al (1998) Short-term vs. long-term dexamethasone treatment: effects on rat diaphragm structure and function. Lung 176:267–280
32.
go back to reference Wilcox PG, Hards JM, Bockhold K, Bressler B, Pardy RL (1989) Pathologic changes and contractile properties of the diaphragm in corticosteroid myopathy in hamsters: comparison to peripheral muscle. Am J Respir Cell Mol Biol 1:191–199 Wilcox PG, Hards JM, Bockhold K, Bressler B, Pardy RL (1989) Pathologic changes and contractile properties of the diaphragm in corticosteroid myopathy in hamsters: comparison to peripheral muscle. Am J Respir Cell Mol Biol 1:191–199
33.
go back to reference Kushmerick MJ, Meyer RA (1985) Chemical changes in rat leg muscle by phosphorus nuclear magnetic resonance. Am J Physiol 248:C542–C549 Kushmerick MJ, Meyer RA (1985) Chemical changes in rat leg muscle by phosphorus nuclear magnetic resonance. Am J Physiol 248:C542–C549
34.
go back to reference Meyer RA, Brown TR, Kushmerick MJ (1985) Phosphorus nuclear magnetic resonance of fast- and slow-twitch muscle. Am J Physiol 248:C279–C287 Meyer RA, Brown TR, Kushmerick MJ (1985) Phosphorus nuclear magnetic resonance of fast- and slow-twitch muscle. Am J Physiol 248:C279–C287
35.
go back to reference Pichard C, Vaughan C, Struk R, Armstrong RL, Jeejeebhoy KN (1988) Effect of dietary manipulations (fasting, hypocaloric feeding, and subsequent refeeding) on rat muscle energetics as assessed by nuclear magnetic resonance spectroscopy. J Clin Invest 82:895–901 Pichard C, Vaughan C, Struk R, Armstrong RL, Jeejeebhoy KN (1988) Effect of dietary manipulations (fasting, hypocaloric feeding, and subsequent refeeding) on rat muscle energetics as assessed by nuclear magnetic resonance spectroscopy. J Clin Invest 82:895–901
36.
go back to reference Thompson A, Damyanovich A, Madapallimattam A, Mikalus D, Allard J, Jeejeebhoy KN (1998) 31P-nuclear magnetic resonance studies of bioenergetic changes in skeletal muscle in malnourished human adults. Am J Clin Nutr 67:39–43 Thompson A, Damyanovich A, Madapallimattam A, Mikalus D, Allard J, Jeejeebhoy KN (1998) 31P-nuclear magnetic resonance studies of bioenergetic changes in skeletal muscle in malnourished human adults. Am J Clin Nutr 67:39–43
37.
go back to reference Gupta RK, Mittal RD, Agarwal KN, Agarwal DK (1994) Muscular sufficiency, serum protein, enzymes and bioenergetic studies (31-phosphorus magnetic resonance spectroscopy) in chronic malnutrition. Acta Paediatr 83:327–331 Gupta RK, Mittal RD, Agarwal KN, Agarwal DK (1994) Muscular sufficiency, serum protein, enzymes and bioenergetic studies (31-phosphorus magnetic resonance spectroscopy) in chronic malnutrition. Acta Paediatr 83:327–331
38.
go back to reference Argov Z, Chance B (1991) Phosphorus magnetic resonance spectroscopy in nutritional research. Annu Rev Nutr 11:449–464CrossRef Argov Z, Chance B (1991) Phosphorus magnetic resonance spectroscopy in nutritional research. Annu Rev Nutr 11:449–464CrossRef
39.
go back to reference Dimitriadis G, Leighton B, Parry-Billings M et al (1997) Effects of glucocorticoid excess on the sensitivity of glucose transport and metabolism to insulin in rat skeletal muscle. Biochem J 321:707–712 Dimitriadis G, Leighton B, Parry-Billings M et al (1997) Effects of glucocorticoid excess on the sensitivity of glucose transport and metabolism to insulin in rat skeletal muscle. Biochem J 321:707–712
40.
go back to reference Leighton B, Challiss RA, Lozeman FJ, Newsholme EA (1987) Effects of dexamethasone treatment on insulin-stimulated rates of glycolysis and glycogen synthesis in isolated incubated skeletal muscles of the rat. Biochem J 246:551–554 Leighton B, Challiss RA, Lozeman FJ, Newsholme EA (1987) Effects of dexamethasone treatment on insulin-stimulated rates of glycolysis and glycogen synthesis in isolated incubated skeletal muscles of the rat. Biochem J 246:551–554
41.
go back to reference Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J Biol Chem 217:383–393 Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J Biol Chem 217:383–393
42.
go back to reference Martens ME, Peterson PL, Lee CP (1991) In vitro effects of glucocorticoid on mitochondrial energy metabolism. Biochim Biophys Acta 1058:152–160 Martens ME, Peterson PL, Lee CP (1991) In vitro effects of glucocorticoid on mitochondrial energy metabolism. Biochim Biophys Acta 1058:152–160
43.
go back to reference Venkatesan N, Davidson MB, Hutchinson A (1987) Possible role for the glucose-fatty acid cycle in dexamethasone-induced insulin antagonism in rats. Metabolism 36:883–891CrossRef Venkatesan N, Davidson MB, Hutchinson A (1987) Possible role for the glucose-fatty acid cycle in dexamethasone-induced insulin antagonism in rats. Metabolism 36:883–891CrossRef
44.
go back to reference Horska A, Brant LJ, Ingram DK, Hansford RG, Roth GS, Spencer RG (1999) Effect of long-term caloric restriction and exercise on muscle bioenergetics and force development in rats. Am J Physiol 276:E766–E773 Horska A, Brant LJ, Ingram DK, Hansford RG, Roth GS, Spencer RG (1999) Effect of long-term caloric restriction and exercise on muscle bioenergetics and force development in rats. Am J Physiol 276:E766–E773
45.
go back to reference Ramsey JJ, Harper ME, Weindruch R (2000) Restriction of energy intake, energy expenditure, and aging. Free Radic Biol Med 29:946–968CrossRef Ramsey JJ, Harper ME, Weindruch R (2000) Restriction of energy intake, energy expenditure, and aging. Free Radic Biol Med 29:946–968CrossRef
46.
go back to reference Koerts-de Lang E, Schols AM, Rooyackers OE, Gayan-Ramirez G, Decramer M, Wouters EF (2000) Different effects of corticosteroid-induced muscle wasting compared with undernutrition on rat diaphragm energy metabolism. Eur J Appl Physiol 82:493–498CrossRef Koerts-de Lang E, Schols AM, Rooyackers OE, Gayan-Ramirez G, Decramer M, Wouters EF (2000) Different effects of corticosteroid-induced muscle wasting compared with undernutrition on rat diaphragm energy metabolism. Eur J Appl Physiol 82:493–498CrossRef
Metadata
Title
Dexamethasone impairs muscle energetics, studied by 31P NMR, in rats
Authors
J.-F. Dumas
G. Bielicki
J.-P. Renou
D. Roussel
P.-H. Ducluzeau
Y. Malthièry
G. Simard
P. Ritz
Publication date
01-02-2005
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 2/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1631-0

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