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Published in: Diabetologia 6/2006

01-06-2006 | Article

The equivocal metabolic response to endotoxaemia in type 2 diabetic and obese ZDF rats

Authors: L. Belabed, G. Senon, M.-C. Blanc, A. Paillard, L. Cynober, S. Darquy

Published in: Diabetologia | Issue 6/2006

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Abstract

Aims/hypothesis

The metabolic and endocrine disturbances associated with obesity and type 2 diabetes may impair the normal metabolic response to injury. Our objective was to investigate amino acid metabolism in endotoxaemic type 2 diabetic obese rats.

Materials and methods

A metabolic study was performed over 4 days using male Zucker diabetic fatty (ZDF) rats (fa/fa) and lean littermates (fa/+) divided into three groups: ad libitum-fed groups which underwent no treatment, lipopolysaccharide (LPS)-treated groups receiving E. coli LPS by i.p. injection, and pair-fed groups to the respective LPS groups. We evaluated the effect of endotoxaemia on body weight, food intake and tissue weights. Nitrogen loss and muscular proteolysis were measured daily by determination of urinary 3-methylhistidine (3-MH) excretion. Plasma, intestine and muscle amino acid levels were measured.

Results

The data showed that ad libitum-fed ZDF rats had lower plasma arginine and glutamine levels than ad libitum-fed control rats. Compared with control rats, the LPS-treated ZDF rats presented lower thymic involution, a lower 3-MH:creatinine ratio and higher cumulative nitrogen balance.

Conclusions/interpretation

Against our working hypothesis, ZDF rats did not show an impaired metabolic response, and even appeared to be less sensitive to the stress.
Literature
2.
go back to reference Dhatariya K, Sreekumaran Nair K (2004) Diabetes mellitus. In: Cynober L (ed.) Metabolic and therapeutics aspects of amino acids in clinical nutrition. CRC, Boca Raton, Florida, pp 355–373 Dhatariya K, Sreekumaran Nair K (2004) Diabetes mellitus. In: Cynober L (ed.) Metabolic and therapeutics aspects of amino acids in clinical nutrition. CRC, Boca Raton, Florida, pp 355–373
4.
go back to reference Biolo G, Toigo G, Ciocchi B et al (1997) Metabolic response to injury and sepsis: changes in protein metabolism. Nutrition 13:52S–57SPubMedCrossRef Biolo G, Toigo G, Ciocchi B et al (1997) Metabolic response to injury and sepsis: changes in protein metabolism. Nutrition 13:52S–57SPubMedCrossRef
5.
go back to reference Van Den Berghe G, Wouters P, Weekers F et al (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345:1359–1367PubMedCrossRef Van Den Berghe G, Wouters P, Weekers F et al (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345:1359–1367PubMedCrossRef
6.
go back to reference Chiolero RL, Tappy L, Berger MM (2003) Nutritional support of obese critically ill patients. Nestle Nutrition Workshop Series. Clinical and Performance Programme 187–200 Chiolero RL, Tappy L, Berger MM (2003) Nutritional support of obese critically ill patients. Nestle Nutrition Workshop Series. Clinical and Performance Programme 187–200
7.
go back to reference De Bandt JP (2004) Insulin and the regulation of amino acid catabolism and protein turnover. In: Cynober L (ed.) Metabolic and therapeutics aspects of amino acids in clinical nutrition. CRC, Boca Raton, Florida, pp 355–373 De Bandt JP (2004) Insulin and the regulation of amino acid catabolism and protein turnover. In: Cynober L (ed.) Metabolic and therapeutics aspects of amino acids in clinical nutrition. CRC, Boca Raton, Florida, pp 355–373
8.
go back to reference Peterson RG, Shaw WN, Neel M-A et al (1990) Zucker diabetic fatty rat as a model for non-insulin-dependent diabetes mellitus. ILAR News 32:16–19 Peterson RG, Shaw WN, Neel M-A et al (1990) Zucker diabetic fatty rat as a model for non-insulin-dependent diabetes mellitus. ILAR News 32:16–19
9.
go back to reference Unger RH (1997) How obesity causes diabetes in Zucker diabetic fatty rats. Trends Endocrinol Metab 8:276–282PubMedCrossRef Unger RH (1997) How obesity causes diabetes in Zucker diabetic fatty rats. Trends Endocrinol Metab 8:276–282PubMedCrossRef
10.
go back to reference Pernet P, Coudray-Lucas C, Schneid C, Jardel A, Cynober L (2004) Dose dependency of the effect of ornithine alpha-ketoglutarate on tissue glutamine concentrations and hypercatabolic response in endotoxaemic rats. Br J Nutr 92:627–634PubMedCrossRef Pernet P, Coudray-Lucas C, Schneid C, Jardel A, Cynober L (2004) Dose dependency of the effect of ornithine alpha-ketoglutarate on tissue glutamine concentrations and hypercatabolic response in endotoxaemic rats. Br J Nutr 92:627–634PubMedCrossRef
11.
go back to reference Loi C, Osowska S, Neveux N, Darquy S, Cynober L, Moinard C (2005) Effects of an immune-enhancing diet in endotoxemic rats. Nutrition 21:255–263PubMedCrossRef Loi C, Osowska S, Neveux N, Darquy S, Cynober L, Moinard C (2005) Effects of an immune-enhancing diet in endotoxemic rats. Nutrition 21:255–263PubMedCrossRef
12.
go back to reference Schlegel L, Coudray-Lucas C, Barbut F, Le Boucher J, Pernet P, Cynober L (1999) Bacterial dissemination, rather than translocation, mediates hypermetabolic response in endotoxemic rats. Crit Care Med 27:1511–1516PubMedCrossRef Schlegel L, Coudray-Lucas C, Barbut F, Le Boucher J, Pernet P, Cynober L (1999) Bacterial dissemination, rather than translocation, mediates hypermetabolic response in endotoxemic rats. Crit Care Med 27:1511–1516PubMedCrossRef
13.
go back to reference Wijekoon EP, Skinner C, Brosnan ME, Brosnan JT (2004) Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes. Can J Physiol Pharmacol 82:506–514PubMedCrossRef Wijekoon EP, Skinner C, Brosnan ME, Brosnan JT (2004) Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes. Can J Physiol Pharmacol 82:506–514PubMedCrossRef
14.
go back to reference Young VR, Munro HN (1978) Ntau-methylhistidine (3-methylhistidine) and muscle protein turnover: an overview. Fed Proc 37:2291–2300PubMed Young VR, Munro HN (1978) Ntau-methylhistidine (3-methylhistidine) and muscle protein turnover: an overview. Fed Proc 37:2291–2300PubMed
15.
go back to reference Blanc MC, Neveux N, Laromiguiere M, Berard MP, Cynober L (2000) Evaluation of a newly available biochemical analyzer: the Olympus AU 600. Clin Chem Lab Med 38:465–475PubMedCrossRef Blanc MC, Neveux N, Laromiguiere M, Berard MP, Cynober L (2000) Evaluation of a newly available biochemical analyzer: the Olympus AU 600. Clin Chem Lab Med 38:465–475PubMedCrossRef
16.
go back to reference Grimble GK, West MF, Acuti AB et al (1988) Assessment of an automated chemiluminescence nitrogen analyzer for routine use in clinical nutrition. JPEN J Parenter Enteral Nutr 12:100–106PubMedCrossRef Grimble GK, West MF, Acuti AB et al (1988) Assessment of an automated chemiluminescence nitrogen analyzer for routine use in clinical nutrition. JPEN J Parenter Enteral Nutr 12:100–106PubMedCrossRef
17.
go back to reference Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126:131–138PubMedCrossRef Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126:131–138PubMedCrossRef
18.
go back to reference Unger RH, Orci L (2001) Diseases of liporegulation: new perspective on obesity and related disorders. FASEB J 15:312–321PubMedCrossRef Unger RH, Orci L (2001) Diseases of liporegulation: new perspective on obesity and related disorders. FASEB J 15:312–321PubMedCrossRef
19.
go back to reference Blanc MC, Moinard C, Béziel A, Darquy S, Cynober L, De Bandt JP (2004) Arginine and glutamine availability and macrophage functions in the obese insulin-resistant Zucker rat. J Cell Physiol 202:153–159CrossRef Blanc MC, Moinard C, Béziel A, Darquy S, Cynober L, De Bandt JP (2004) Arginine and glutamine availability and macrophage functions in the obese insulin-resistant Zucker rat. J Cell Physiol 202:153–159CrossRef
20.
go back to reference Long K, Tayek JA (1999) Are gluconeogenic amino acids reduced in obese and non-obese type 2 diabetic patients (DM-2) compared to weight similar normal volunteers? Diabetes 48:A460–A461CrossRef Long K, Tayek JA (1999) Are gluconeogenic amino acids reduced in obese and non-obese type 2 diabetic patients (DM-2) compared to weight similar normal volunteers? Diabetes 48:A460–A461CrossRef
21.
go back to reference Morris SM J (2000) Regulation of arginine availability and its impact on NO synthesis. In: Ignarro JL (ed) Nitric oxide: biology and pathobiology. Academic, San Diego, California, pp 187–197 Morris SM J (2000) Regulation of arginine availability and its impact on NO synthesis. In: Ignarro JL (ed) Nitric oxide: biology and pathobiology. Academic, San Diego, California, pp 187–197
22.
go back to reference Fu WJ, Haynes TE, Kohli R et al (2005) Dietary l-arginine supplementation reduces fat mass in Zucker diabetic fatty rats. J Nutr 135:714–721PubMed Fu WJ, Haynes TE, Kohli R et al (2005) Dietary l-arginine supplementation reduces fat mass in Zucker diabetic fatty rats. J Nutr 135:714–721PubMed
23.
go back to reference Stumvoll M, Perriello G, Nurjhan N et al (1996) Glutamine and alanine metabolism in NIDDM. Diabetes 45:863–868PubMedCrossRef Stumvoll M, Perriello G, Nurjhan N et al (1996) Glutamine and alanine metabolism in NIDDM. Diabetes 45:863–868PubMedCrossRef
24.
go back to reference Brosnan JT, Man KC, Hall DE, Colbourne SA, Brosnan ME (1983) Interorgan metabolism of amino acids in streptozotocin-diabetic ketoacidotic rat. Am J Physiol 244:E151–E158PubMed Brosnan JT, Man KC, Hall DE, Colbourne SA, Brosnan ME (1983) Interorgan metabolism of amino acids in streptozotocin-diabetic ketoacidotic rat. Am J Physiol 244:E151–E158PubMed
25.
go back to reference Rodriguez T, Alvarez B, Busquets S, Carbo N, Lopez-Soriano FJ, Argiles JM (1997) The increased skeletal muscle protein turnover of the streptozotocin diabetic rat is associated with high concentrations of branched-chain amino acids. Biochem Mol Med 61:87–94PubMedCrossRef Rodriguez T, Alvarez B, Busquets S, Carbo N, Lopez-Soriano FJ, Argiles JM (1997) The increased skeletal muscle protein turnover of the streptozotocin diabetic rat is associated with high concentrations of branched-chain amino acids. Biochem Mol Med 61:87–94PubMedCrossRef
26.
go back to reference Nair KS, Short KR (2005) Hormonal and signaling role of branched-chain amino acids. J Nutr 135:1547S–1552SPubMed Nair KS, Short KR (2005) Hormonal and signaling role of branched-chain amino acids. J Nutr 135:1547S–1552SPubMed
27.
go back to reference Manco M, Mingrone G (2005) Effects of weight loss and calorie restriction on carbohydrate metabolism. Curr Opin Clin Nutr Metab Care 8:431–439PubMedCrossRef Manco M, Mingrone G (2005) Effects of weight loss and calorie restriction on carbohydrate metabolism. Curr Opin Clin Nutr Metab Care 8:431–439PubMedCrossRef
28.
go back to reference Marchesini G, Bianchi GP, Vilstrup H, Capelli M, Zoli M, Pisi E (1991) Elimination of infused branched-chain amino-acids from plasma of patients with non-obese type 2 diabetes mellitus. Clin Nutr 10:105–113PubMedCrossRef Marchesini G, Bianchi GP, Vilstrup H, Capelli M, Zoli M, Pisi E (1991) Elimination of infused branched-chain amino-acids from plasma of patients with non-obese type 2 diabetes mellitus. Clin Nutr 10:105–113PubMedCrossRef
29.
go back to reference Freyse EJ, Fischer U, Knospe S, Ford GC, Nair KS (2006) Differences in protein and energy metabolism following portal versus systemic administration of insulin in diabetic dogs. Diabetologia 49:543–551PubMedCrossRef Freyse EJ, Fischer U, Knospe S, Ford GC, Nair KS (2006) Differences in protein and energy metabolism following portal versus systemic administration of insulin in diabetic dogs. Diabetologia 49:543–551PubMedCrossRef
30.
go back to reference Lasnier E, Coudray-Lucas C, Le Boucher J, Jardel A, Cynober L (1997) Ornithine a-ketoglutarate counteracts thymus involution and glutamine depletion in endotoxemic rats. Clin Nutr 77:197–200 Lasnier E, Coudray-Lucas C, Le Boucher J, Jardel A, Cynober L (1997) Ornithine a-ketoglutarate counteracts thymus involution and glutamine depletion in endotoxemic rats. Clin Nutr 77:197–200
31.
go back to reference Breuille D, Voisin L, Contrepois M, Arnal M, Rose F, Obled C (1999) A sustained rat model for studying the long-lasting catabolic state of sepsis. Infect Immun 67:1079–1085PubMed Breuille D, Voisin L, Contrepois M, Arnal M, Rose F, Obled C (1999) A sustained rat model for studying the long-lasting catabolic state of sepsis. Infect Immun 67:1079–1085PubMed
32.
go back to reference Cooney RN, Kimball SR, Vary TC (1997) Regulation of skeletal muscle protein turnover during sepsis: mechanisms and mediators. Shock 7:1–16PubMedCrossRef Cooney RN, Kimball SR, Vary TC (1997) Regulation of skeletal muscle protein turnover during sepsis: mechanisms and mediators. Shock 7:1–16PubMedCrossRef
34.
go back to reference Abumrad N, Barbul A (2003) The use of arginine in clinical practice. In: Cynober L (ed.) Metabolic and therapeutics aspects of amino acids in clinical nutrition. CRC, Boca Raton, Florida, pp 355–373 Abumrad N, Barbul A (2003) The use of arginine in clinical practice. In: Cynober L (ed.) Metabolic and therapeutics aspects of amino acids in clinical nutrition. CRC, Boca Raton, Florida, pp 355–373
35.
go back to reference Long CL, Birkhahn RH, Geiger JW, Betts JE, Schiller WR, Blakemore WS (1981) Urinary excretion of 3-methylhistidine: an assessment of muscle protein catabolism in adult normal subjects and during malnutrition, sepsis, and skeletal trauma. Metabolism 30:765–776PubMedCrossRef Long CL, Birkhahn RH, Geiger JW, Betts JE, Schiller WR, Blakemore WS (1981) Urinary excretion of 3-methylhistidine: an assessment of muscle protein catabolism in adult normal subjects and during malnutrition, sepsis, and skeletal trauma. Metabolism 30:765–776PubMedCrossRef
36.
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 24:30–36PubMedCrossRef 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 24:30–36PubMedCrossRef
37.
go back to reference Mills CD (2001) Macrophage arginine metabolism to ornithine/urea or nitric oxide/citrulline: a life or death issue. Crit Rev Immunol 21:399–426PubMed Mills CD (2001) Macrophage arginine metabolism to ornithine/urea or nitric oxide/citrulline: a life or death issue. Crit Rev Immunol 21:399–426PubMed
38.
go back to reference Austgen TR, Chakrabarti R, Chen MK, Souba WW (1992) Adaptive regulation in skeletal muscle glutamine metabolism in endotoxin-treated rats. J Trauma 32:600–606PubMedCrossRef Austgen TR, Chakrabarti R, Chen MK, Souba WW (1992) Adaptive regulation in skeletal muscle glutamine metabolism in endotoxin-treated rats. J Trauma 32:600–606PubMedCrossRef
39.
go back to reference Parry-Billings M, Leighton B, Dimitriadis G, de Vasconcelos PR, Newsholme EA (1989) Skeletal muscle glutamine metabolism during sepsis in the rat. Int J Biochem 21:419–423PubMedCrossRef Parry-Billings M, Leighton B, Dimitriadis G, de Vasconcelos PR, Newsholme EA (1989) Skeletal muscle glutamine metabolism during sepsis in the rat. Int J Biochem 21:419–423PubMedCrossRef
40.
go back to reference Darmaun D (1999) Role of nutrients in the regulation of in vivo protein metabolism in humans. Acta Paediatr Suppl 88:92–94PubMedCrossRef Darmaun D (1999) Role of nutrients in the regulation of in vivo protein metabolism in humans. Acta Paediatr Suppl 88:92–94PubMedCrossRef
41.
go back to reference Jeevanandam M, Ramias L, Schiller WR (1991) Altered plasma free amino acid levels in obese traumatized man. Metabolism 40:385–390PubMedCrossRef Jeevanandam M, Ramias L, Schiller WR (1991) Altered plasma free amino acid levels in obese traumatized man. Metabolism 40:385–390PubMedCrossRef
42.
go back to reference Jeevanandam M, Young DH, Schiller WR (1991) Obesity and the metabolic response to severe multiple trauma in man. J Clin Invest 87:262–269PubMedCrossRef Jeevanandam M, Young DH, Schiller WR (1991) Obesity and the metabolic response to severe multiple trauma in man. J Clin Invest 87:262–269PubMedCrossRef
43.
go back to reference Forbes GB, Drenick EJ (1979) Loss of body nitrogen on fasting. Am J Clin Nutr 32:1570–1574PubMed Forbes GB, Drenick EJ (1979) Loss of body nitrogen on fasting. Am J Clin Nutr 32:1570–1574PubMed
44.
go back to reference Leiter LA, Marliss EB (1982) Survival during fasting may depend on fat as well as protein stores. JAMA 248:2306–2307PubMedCrossRef Leiter LA, Marliss EB (1982) Survival during fasting may depend on fat as well as protein stores. JAMA 248:2306–2307PubMedCrossRef
45.
go back to reference Elia M, Stubbs RJ, Henry CJ (1999) Differences in fat, carbohydrate, and protein metabolism between lean and obese subjects undergoing total starvation. Obes Res 7:597–604PubMed Elia M, Stubbs RJ, Henry CJ (1999) Differences in fat, carbohydrate, and protein metabolism between lean and obese subjects undergoing total starvation. Obes Res 7:597–604PubMed
46.
go back to reference Tessari P, Nissen SL, Miles JM, Haymond MW (1986) Inverse relationship of leucine flux and oxidation to free fatty acid availability in vivo. J Clin Invest 77:575–581PubMedCrossRef Tessari P, Nissen SL, Miles JM, Haymond MW (1986) Inverse relationship of leucine flux and oxidation to free fatty acid availability in vivo. J Clin Invest 77:575–581PubMedCrossRef
47.
go back to reference Beaufrere B, Chassard D, Broussole C, Riou JP, Beylot M (1992) Effects of d-beta-hydroxy-butyrate, long and medium chain triglycerides on leucine metabolism in man. Am J Physiol 262:E268–E274PubMed Beaufrere B, Chassard D, Broussole C, Riou JP, Beylot M (1992) Effects of d-beta-hydroxy-butyrate, long and medium chain triglycerides on leucine metabolism in man. Am J Physiol 262:E268–E274PubMed
Metadata
Title
The equivocal metabolic response to endotoxaemia in type 2 diabetic and obese ZDF rats
Authors
L. Belabed
G. Senon
M.-C. Blanc
A. Paillard
L. Cynober
S. Darquy
Publication date
01-06-2006
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 6/2006
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0233-4

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