Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-14T09:50:57.444Z Has data issue: false hasContentIssue false
  • English
  • Français

Kinetics of dodecanedioic acid and effect of its administration on glucose kinetics in rats

Published online by Cambridge University Press:  09 March 2007

Alessandro Bertuzzi ,
Geltrude Mingrone ,
Andrea De Gaetano ,
Alberto Gandolfi ,
Aldo V Greco  and
Serenella Salinari
Alessandro Bertuzzi
Affiliation:
Istituto di Analisi dei Sistemi ed Informatica del CNR, Viale Manzoni 30, 00185, Roma, Italy
Geltrude Mingrone
Affiliation:
Istituto di Clinica Medica, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Roma, Italy
Andrea De Gaetano
Affiliation:
Centro di Studio per la Fisiopatologia dello Shock del CNR, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Roma, Italy
Alberto Gandolfi
Affiliation:
Istituto di Analisi dei Sistemi ed Informatica del CNR, Viale Manzoni 30, 00185, Roma, Italy
Aldo V Greco
Affiliation:
Istituto di Clinica Medica, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Roma, Italy
Serenella Salinari
Affiliation:
Dipartimento di Informatica e Sistemistica, Università di Roma ‘La Sapienza’, Roma, Italy
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Dodecanedioic acid (C12), a saturated aliphatic dicarboxylic acid with twelve C atoms, was given as an intraperitoneal bolus to male Wistar rats, with the aim of evaluating C12 suitability as an energy substrate for parenteral nutrition. The 24 h urinary excretion of C12 was 3·9% of the administered dose. C12 kinetics were investigated by a one-compartment model with saturable tissue uptake and reversible binding to plasma albumin. The analysis of plasma concentration and urinary excretion data from different animals yielded the population means of the kinetic parameters: renal clearance was 0·72ml/min per kg body weight (BW) (much smaller than inulin clearance in the rat), and maximal tissue uptake was 17·8 μmol/min per kg BW corresponding to 123·7 J/min per kg BW. These results encourage the consideration of C12 as a possible substrate for parenteral nutrition. To investigate the effect of C12 administration on glucose kinetics, two other groups of rats, one treated with an intraperitoneal bolus of C12 and the other with saline, were subsequently given an intravenous injection of D-[U-14C]glucose in a tracer amount. Radioactivity data of both control and C12-treated rats were analysed by means of a two-compartment kinetic model which takes into account glucose recycling. The estimates of glucose pool size (2·3 mmol/kg BW) and total-body rate of disappearance (82·1 μmol/min per kg BW) in control rats agreed with published values. In C12-treated rats, the rate of disappearance appeared to be reduced to 36·7 μmol/min per kg BW and the extent of recycling appeared to be negligible.

Keywords

Dodecanedioic acidGlucoseParenteral nutrition
Type
General Nutrition
Information
British Journal of Nutrition , Volume 78 , Issue 1 , July 1997 , pp. 143 - 153
Copyright
Copyright © The Nutrition Society 1997

References

REFERENCES

Akaike, H. (1974). A new look at the statistical model identification. IEEE Transactions on Automatic Control AC-19, 716–723.CrossRefGoogle Scholar
Baker, N., Shipley, R. A., Clark, R. E. & Incefy, G. E. (1959). C14 studies in carbohydrate metabolism: glucose pool size and rate of turnover in the normal rat. American Journal of Physiology 196, 245–252.CrossRefGoogle ScholarPubMed
Bertuzzi, A., Gandolfi, A., Salinari, S., Mingrone, G., Arcieri-Mastromattei, E., Finotti, E. & Greco, A. V. (1991). Pharmacokinetic analysis of azelaic acid disodium salt. Clinical Pharmacokinetics 20, 411–419.Google Scholar
Bertuzzi, A., Mingrone, G., Gandolfi, A., Greco, A. V. & Salinari, S. (1995). Pharmacokinetic analysis of dodecanedioic acid in humans from bolus data. Journal of Parenteral and Enteral Nutrition 19, 498–501.CrossRefGoogle ScholarPubMed
Bjorkhem, I. (1978). On the quantitative importance of ω-oxidation of fatty acids. Journal of Lipid Research 19, 585–590.Google Scholar
Borst, P., Loos, J. A., Crist, E. J. & Slater, E. C. (1962). Uncoupling activity of long-chain fatty acids. Biochimica et Biophysica Acta 62, 509–518.CrossRefGoogle ScholarPubMed
Greco, A. V. & Mingrone, G. (1995). Dicarboxylic acids, an alternate fuel substrate in parenteral nutrition: an update. Clinical Nutrition 14, 143–148.CrossRefGoogle Scholar
James, D. E., Burleigh, K. M. & Kraegen, E. W. (1986). In vivo glucose metabolism in individual tissues of the rat. Interaction between epinephrine and insulin. Journal of Biological Chemistry 261, 6366–6374.CrossRefGoogle Scholar
Jenkins, A. B., Storlien, L. H., Chisholm, D. J. & Kraegen, E. W. (1988). Effects of nonesterified fatty acid availability on tissue-specific glucose utilization in rats in vivo. Journal of Clinical Investigation 82, 293–299.Google Scholar
Katz, J., Dunn, A., Chenoweth, M. & Golden, S. (1974). Determination of synthesis, recycling and body mass of glucose in rats and rabbits in vivo with 3H- and 14C-labelled glucose. Biochemical Journal 142, 171–183.CrossRefGoogle ScholarPubMed
Kou, Y. & Tsemg, J. Shiow-Jen (1991). Metabolic conversion of dicarboxylic acids to succinate in rat liver homogenates. Journal of Biological Chemistry 266, 2924–2929.Google Scholar
Leighton, F., Bergseth, S., Rortveit, T., Christiansen, E. N. & Bremer, J. (1989). Free acetate production by rat hepatocytes during peroxisomal fatty acid and dicarboxylic acid oxidation. Journal of Biological Chemistry 264, 10346–10350.Google Scholar
Lindstedt, S., Norberg, K., Steen, G. & Wahl, E. (1976). Structure of some aliphatic dicarboxylic acids found in the urine of an infant with congenital lactic acidosis. Clinical Chemistry 22, 1330–1338.Google Scholar
Mingrone, G., Greco, A. V. & Arcieri-Mastromattei, E. (1990). Free fatty acids stimulate mucin hypersecretion by rabbit gallbladder epithelium in vitro. Clinical Science 78, 175–180.CrossRefGoogle ScholarPubMed
Mingrone, G., Greco, A. V., Bertuzzi, A., Arcieri-Mastromattei, E., Tacchino, R. M., Marino, F., Finotti, E. & Castagneto, M. (1991). Tissue uptake and oxidation of disodium sebacate in man. Journal of Parenteral and Enteral Nutrition 15, 454–459.CrossRefGoogle ScholarPubMed
Mingrone, G., Greco, A. v, De Gaetano, A., Tataranni, A., Raguso, C. & Castagneto, M. (1994). Pharmacokinetic profile of dodecanedioic acid, a proposed alternative lipid substrate for parenteral nutrition. Journal of Parenteral and Enteral Nutrition 18, 225–230.Google Scholar
Mingrone, G., Tacchino, R. M., Greco, A. V., Arcieri-Mastromattei, E., Marino, F., Finotti, E. & Castagneto, M. (1989). Preliminary studies of a dicarboxylic acid as an energy substrate in man. Journal of Parenteral and Enteral Nutrition 13, 299–305.Google Scholar
Mortensen, P. G. & Gregersen, N. (1981). The biological origin of ketonic dicarboxylic aciduria. In vivo and in vitro investigations of the ω-oxidation of C6-C10-monocarboxylic acids in unstarved, starved and diabetic rats. Biochimica et Biophysica Acta 666, 394–404.CrossRefGoogle Scholar
Pettersen, J. E. & Aas, M. (1973). ATP-dependent activation of dicarboxylic acids in rat liver. Biochimica et Biophysica Acta 326, 305–313.Google Scholar
Raguso, C., Mingrone, G., Greco, A. v., Tataranni, P. A., De Gaetano, A. & Castagneto, M. (1994). Dicarboxylic acids and glucose utilization in humans: effect of sebacate. Journal of Parenteral and Enteral Nutrition 18, 9–13.Google Scholar
Royle, G. T., Wolfe, R. R. & Burke, J. F. (1982). Glucose and fatty acid kinetics in fasted rats: effects of previous protein intake. Metabolism 31, 279–283.CrossRefGoogle ScholarPubMed
Seber, G. A. F. & Wild, C. J. (1989). Nonlinear Regression. New York: Wiley.CrossRefGoogle Scholar
Verkade, P. E. & Van der Lee, J. (1934). Researches on fat metabolism II. Biochemical Journal 28, 31–40.Google Scholar
Wada, F. & Usami, M. (1977). Studies on fatty acid omega-oxidation. Antiketogenic effect and gluconeogenicity of dicarboxylic acids. Biochimica et Biophysica Acta 487, 261–268.CrossRefGoogle ScholarPubMed
Wyngaarden, J. B. & Smith, L. H. (editors) (1995). Cecil Textbook of Medicine. Philadelphia: W. B. Saunders Company.Google Scholar
Zweig, G. & Sherma, J. (editors) (1972). CRC Handbook of Chromatography: General Data and Principles, vol. 1, pp. 462–463. Boca Raton, FL: CRC Press.Google Scholar