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Horm Metab Res 2001; 33(8): 463-466
DOI: 10.1055/s-2001-16938
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Oxidation of D-[U -14C] Glucose and [1,12 -14C] Dodecanedioic Acid by Pancreatic Islets from Goto-Kakizaki Rats

W. J. Malaisse1 , M. Doherty1 , L. Ladrière1 , A. V. Greco2 , G. Mingrone2
  • 1 Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium
  • 2 Instituto de Clinica Medica, Universita Cattolica del Sacro Cuore, Roma, Italy
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Publication History

Publication Date:
04 September 2001 (online)

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In pancreatic islets from hereditarily diabetic GK rats, [1,12 -14C] dodecanedioic acid (5.0 mM) was oxidized at a rate representing about 5 % of that of D-[U - 14C] glucose (8.3 mM). Dioic acid and hexose failed to exert any significant reciprocal effects on their respective oxidation. The production of 14CO2 from [1,12 -14C] dodecanedioic acid was proportional to its concentration in the 0.2 - 5.0 mM range. These results were essentially comparable to those obtained in islets from control rats. They extend, therefore, to GK rats the knowledge that dodecanedioic acid acts as a nutrient in pancreatic islet cells.

Key words:

 [1,12 -14C] Dodecanedioic Acid - Pancreatic Islets - GK Rats

References

  • 1 Greco A V, Mingrone G. Dicarboxylic acids, an alternate fuel substrate in parenteral nutrition: an update.  Clinical Nutrition. 1995;  14 143-148
    CrossrefPubMedSearch in Google Scholar
  • 2 Leighton F, Bergseth S, Rortveit T, Christiansen E N, Bremer J. Free acetate production by rat hepatocytes during peroxisomal fatty acid and dicarboxylic acid oxidation.  J Biol Chem. 1989;  264 10 346-10 350
    PubMedSearch in Google Scholar
  • 3 Mortersen P B, Kølvraa S, Gregersen N. Cyanide insensitive and clofibrate enhanced β-oxidation of dodecanedioic acid: evidence of peroxisomal β-oxidation of dicarboxylic acids.  Biochim Biophys Acta. 1982;  713 393-397
    PubMedSearch in Google Scholar
  • 4 Pettersen J E. Metabolism of hexadecanedioic acid and its mono-L-carnitine ester.  Biochim Biophys Acta. 1973;  306 1-19
    PubMedSearch in Google Scholar
  • 5 Vamecq J, Draye J P. Peroxisomal and mitochondrial β-oxidation of monocarboxylyl-CoA, ω-hydroxymonocarboxylyl-CoA and dicarboxylyl-CoA esters in tissues from untreated and clofibrate-treated rats.  J Biochem. 1989;  106 216-222
    PubMedSearch in Google Scholar
  • 6 Kou Y, Tserng Shiow-Jen J. Metabolic conversion of dicarboxylic acids to succinate in rat liver homogenates.  J Biol Chem. 1991;  266 2924-2929
    PubMedSearch in Google Scholar
  • 7 Saint-Macary M, Foucher B. Comparative partial purification of the active dicarboxylate transport system of rat liver, kidney and heart mitochondria.  Biochem Biophys Res Commun. 1985;  133 498-504
    CrossrefPubMedSearch in Google Scholar
  • 8 Boelsterli U A, Zimmerli B, Meier P J. Identification and characterization of a basolateral dicarboxylate/cholate antiport system in rat hepatocytes.  Am J Physiol. 1995;  268 G797-G805
    PubMedSearch in Google Scholar
  • 9 Sheridan E, Rumrich G, Ullrich K J. Reabsorption of dicarboxylic acids from the proximal convolution of rat kidney.  Pfluegers Arch. 1983;  399 18-28
    CrossrefPubMedSearch in Google Scholar
  • 10 Ullrich K J, Fasold H, Rumrich G, Kloss S. Secretion and contraluminal uptake of dicarboxylic acids in the proximal convolution of rat kidney.  Pfluegers Arch. 1984;  400 241-249
    CrossrefPubMedSearch in Google Scholar
  • 11 Bertuzzi A, Mingrone G, Gandolfi A, Greco A V, Salinari S. Disposition of dodecanedioic acid in humans.  J Pharmacol Exper Ther. 2000;  292 846-852
    PubMedSearch in Google Scholar
  • 12 Raguso C A, Mingrone G, Greco A V, Tataranni P A, DeGaetano A, Castagneto M. Dicarboxylic acids and glucose utilization in humans: effect of sebacate.  JPEN. 1994;  18 9-13
    PubMedSearch in Google Scholar
  • 13 Greco A V, Mingrone G, Capristo E, Benedetti G, DeGaetano A, Gasbarrini G. The metabolic effect of dodecanedioic acid infusion in non-insulin-dependent diabetic patients.  Nutrition. 1998;  14 351-357
    CrossrefPubMedSearch in Google Scholar
  • 14 Beck-Nielsen H. Insulin resistance in skeletal muscles of patients in diabetes mellitus.  Diabetes Metab Rev. 1989;  5 487-493
    PubMedSearch in Google Scholar
  • 15 Falholt K, Jensens I, Lindkaer Jensen S, Mortensen H, Volund A, Heding L G, Noerskov Petersen P, Falholt W. Carbohydrate and lipid metabolism of skeletal muscle in type 2 diabetes patients.  Diabet Med. 1988;  5 27-31
    PubMedSearch in Google Scholar
  • 16 Malaisse W J, Greco A V, Mingrone G. Effects of aliphatic dioic acids and glycerol-1,2,3-tris(dodecanedioate) on D-glucose-stimulated insulin release in rat pancreatic islets.  Br J Nutr . 2000;  84 733-736
    PubMedSearch in Google Scholar
  • 17 Malaisse W J, Greco A V, Mingrone G. Oxidation of [1,12 -14C] dodecanedioic acid by rat pancreatic islets.  Int J Mol Med. 2000;  6 453-454
    PubMedSearch in Google Scholar
  • 18 Goto Y, Kakizaki M, Masaki N. Spontaneous diabetes produced by selective breeding of normal Wistar rats.  Proc Jpn Acad. 1975;  51 80-85
    PubMedSearch in Google Scholar
  • 19 Malaisse W J, Sener A. Hexose metabolism in pancreatic islets. Feedback control of D-glucose oxidation by functional events.  Biochim Biophys Acta. 1988;  971 246-254
    PubMedSearch in Google Scholar
  • 20 Bjorklund A, Yaney G, McGarry J D, Weir G. Fatty acids and β-cell function.  Diabetologia. 1997;  40 (Suppl 3) B21-B26
    CrossrefPubMedSearch in Google Scholar
  • 21 Lee Y, Hirose H, Ohneda M, Johnson J H, McGarry J D, Unger R H. β-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte β-cell relationships.  Proc Natl Acad Sci USA. 1994;  91 10878-10 882
    PubMedSearch in Google Scholar
  • 22 Milburn J L, Hirose H, Lee Y H, Nagasawa Y, Ogawa A, Ohneda M, BeltrandelRio H, Newgard C B, Johnson J H, Unger R H. Pancreatic β-cells in obesity. Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids.  J Biol Chem. 1995;  270 1295-1299
    CrossrefPubMedSearch in Google Scholar
  • 23 Prentki M, Corkey B E. Are the β-cell signaling molecules malonyl-CoA and cytosolic long-chain acyl-CoA implicated in multiple tissue defects of obesity and NIDDM?.  Diabetes. 1996;  45 273-283
    CrossrefPubMedSearch in Google Scholar
  • 24 Unger R. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM.  Diabetes. 1995;  44 863-870
    PubMedSearch in Google Scholar
  • 25 Chen S, Ogawa A, Ohneda M, Unger R H, Foster D W, McGarry J D. More direct evidence for a malonyl-CoA-carnitine palmitoyltransferase I interaction as a key event in pancreatic β-cell signaling.  Diabetes. 1994;  43 878-883
    PubMedSearch in Google Scholar
  • 26 Warnotte C, Gilon P, Nenquin M, Henquin J C. Mechanisms of the stimulation of insulin release by saturated fatty acids.  Diabetes. 1994;  43 703-711
    CrossrefPubMedSearch in Google Scholar
  • 27 Crespin S R, Greenough W B, Steinberg D. Stimulation of insulin secretion by long-chain free fatty acids.  J Clin Invest. 1973;  53 1979-1984
    PubMedSearch in Google Scholar
  • 28 Hennes M MI, Dua A, Kissebah A H. Effect of free fatty acids and glucose on splanchnic insulin dynamics.  Diabetes. 1997;  46 57-62
    PubMedSearch in Google Scholar
  • 29 Stein D T, Esser V, Stevenson B E, Lane K E, Whiteside J H, Daniels M B, Chen S, McGarry J D. Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat.  J Clin Invest. 1996;  97 2728-2735
    CrossrefPubMedSearch in Google Scholar
  • 30 Elks M L. Chronic perifusion of rat islets with palmitate suppresses glucose-stimulated insulin release.  Endocrinology. 1993;  133 208-214
    CrossrefPubMedSearch in Google Scholar
  • 31 Zhou Y P, Grill V E. Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle.  J Clin Invest. 1994;  93 870-876
    CrossrefPubMedSearch in Google Scholar
  • 32 Zhou Y P, Grill V. Long-term exposure to fatty acids and ketones inhibits β-cell function in human pancreatic islets of Langerhans.  J Clin Endocrinol Metab. 1995;  80 1575-1580
    PubMedSearch in Google Scholar
  • 33 Zhou Y, Berggren P, Grill V. A fatty acid-induced decrease in pyruvate dehydrogenase activity is an important determinant of β-cell dysfunction in the obese diabetic db/db mouse.  Diabetes. 1996;  45 580-586
    PubMedSearch in Google Scholar
  • 34 Sako Y, Grill V. A 48-hour lipid infusion in the rat time-dependently inhibits glucose-induced insulin secretion and β-cell oxidation through a process likely coupled to fatty acid oxidation.  Endocrinology. 1990;  127 1580-1589
    PubMedSearch in Google Scholar
  • 35 Shimabukuro M, Zhou Y T, Levi M, Unger R H. Fatty acid-induced β-cell apoptosis: A link between obesity and diabetes.  Proc Natl Acad Sci USA. 1998;  95 2498-2502
    CrossrefPubMedSearch in Google Scholar
  • 36 Mingrone G ., De Gaetano A, Greco A V, Capristo E, Benedetti G, Tacchino R M, Castagneto M, Gasbarrini G. Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids.  Diabetologia. 1997;  40 599-605
    CrossrefPubMedSearch in Google Scholar
  • 37 Mingrone G, Henriksen F L, Greco A V, Krogh L N, Capristo E, Benedetti E, Gastaldelli A, Castagneto M, Ferrannini E, Gasbarrini G, Beck-Nielsen H. Triglyceride-induced diabetes associated with familial lipoprotein lipase deficiency.  Diabetes. 1999;  48 1258-1263
    PubMedSearch in Google Scholar
  • 38 Mingrone G, De Gaetano A, Greco A V, Capristo E, Benedetti G, Castagneto M, Gasbarrini G. Dodecanedioic acid infusion induces a sparing effect on whole-body glucose uptake, mainly in non-insulin-dependent diabetes mellitus.  Br J Nutr. 1997;  78 723-735
    CrossrefPubMedSearch in Google Scholar

W. J. Malaisse, M.D., Ph.D.

Laboratory of Experimental Medicine
Brussels Free University

808 Route de Lennik
1070 Brussels
Belgium


Phone: + 32 (2) 5556237

Fax: + 32 (2) 5556239

Email: malaisse@med.ulb.ac.be