Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1995 Feb 1;305(Pt 3):811–816. doi: 10.1042/bj3050811

Tissue differences in the response of the pyruvate dehydrogenase complex to a glucose load during the development of obesity in gold-thioglucose-obese mice.

J M Bryson 1, G J Cooney 1, V R Wensley 1, J L Phuyal 1, I D Caterson 1
PMCID: PMC1136331  PMID: 7848280

Abstract

The activity of pyruvate dehydrogenase (PDHC), a key enzyme complex in the oxidative disposal of glucose, was measured after an oral glucose load in the heart, liver, quadriceps muscle, white adipose tissue (WAT) and brown adipose tissue (BAT) of gold-thioglucose (GTG)-obese mice at different stages during the development of obesity and in age-matched controls. Significant responses to the glucose load were seen 30 min post-gavage in heart, WAT and BAT of control mice but no change was observed in quadriceps muscle. The increase in activity of the active form of PDHC (PDHCa) in response to glucose in heart was reduced 2 weeks after the induction of GTG-obesity with no response in 5 or 10 week obese mice. A 2-3-fold increase in the PDHCa response in both WAT and BAT of 2 week obese mice was absent in 5 and 10 week obese animals. Basal PDHCa activity in quadriceps muscle was increased in 2 week obese mice but subsequently returned to control levels as obesity progressed. The glucose load produced no change in the activity of PDHCa in quadriceps muscle of obese mice. These results demonstrate that changes in the capacity for oxidative glucose disposal in different tissues, as indicated by changes in PDHCa activity, may contribute to glucose-intolerance and insulin-resistance in GTG-obese mice and that the response of the PDHC to insulin during the development of obesity varies in different tissues.

Full text

PDF
811

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blair S. C., Caterson I. D., Cooney G. J. Insulin response to an intravenous glucose load during development of obesity in gold thioglucose-injected mice. Diabetes. 1993 Aug;42(8):1153–1158. doi: 10.2337/diab.42.8.1153. [DOI] [PubMed] [Google Scholar]
  2. Boden G., Jadali F., White J., Liang Y., Mozzoli M., Chen X., Coleman E., Smith C. Effects of fat on insulin-stimulated carbohydrate metabolism in normal men. J Clin Invest. 1991 Sep;88(3):960–966. doi: 10.1172/JCI115399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bryson J. M., Cooney G. J., Wensley V. R., Blair S. C., Caterson I. D. Diurnal patterns of cardiac and hepatic pyruvate dehydrogenase complex activity in gold-thioglucose-obese mice. Biochem J. 1993 Nov 1;295(Pt 3):731–734. doi: 10.1042/bj2950731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Caterson I. D., Astbury L. D., Williams P. F., Vanner M. A., Cooney G. J., Turtle J. R. The activity of the pyruvate dehydrogenase complex in heart and liver from mice during the development of obesity and insulin resistance. Biochem J. 1987 Apr 15;243(2):549–553. doi: 10.1042/bj2430549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Caterson I. D., Williams P. F., Kerbey A. L., Astbury L. D., Plehwe W. E., Turtle J. R. The effect of body weight and the fatty acid-oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in mouse heart. Biochem J. 1984 Dec 15;224(3):787–791. doi: 10.1042/bj2240787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Collier G. R., Traianedes K., Macaulay S. L., O'Dea K. Effect of fatty acid oxidation inhibition on glucose metabolism in diabetic rats. Horm Metab Res. 1993 Jan;25(1):9–12. doi: 10.1055/s-2007-1002035. [DOI] [PubMed] [Google Scholar]
  7. Cooney G. J., Astbury L. D., Williams P. F., Caterson I. D. Insulin response in individual tissues of control and gold thioglucose-obese mice in vivo with [1-14C]2-deoxyglucose. Diabetes. 1987 Feb;36(2):152–158. doi: 10.2337/diab.36.2.152. [DOI] [PubMed] [Google Scholar]
  8. Cooney G. J., Denyer G. S., Jenkins A. B., Storlien L. H., Kraegen E. W., Caterson I. D. In vivo insulin sensitivity of the pyruvate dehydrogenase complex in tissues of the rat. Am J Physiol. 1993 Jul;265(1 Pt 1):E102–E107. doi: 10.1152/ajpendo.1993.265.1.E102. [DOI] [PubMed] [Google Scholar]
  9. Cooney G. J., Denyer G. S., Kerbey A. L., Frankland R. L., Blair S. C., Williams P. F., Caterson I. D. Pyruvate dehydrogenase-complex activity in brown adipose tissue of gold thioglucose-obese mice. Biochem J. 1990 Aug 15;270(1):257–259. doi: 10.1042/bj2700257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cooney G. J., Vanner M. A., Nicks J. L., Williams P. F., Caterson I. D. Changes in the lipogenic response to feeding of liver, white adipose tissue and brown adipose tissue during the development of obesity in the gold-thioglucose-injected mouse. Biochem J. 1989 May 1;259(3):651–657. doi: 10.1042/bj2590651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cousin B., Agou K., Leturque A., Ferre P., Girard J., Pénicaud L. Molecular and metabolic changes in white adipose tissue of the rat during development of ventromedial hypothalamic obesity. Eur J Biochem. 1992 Jul 1;207(1):377–382. doi: 10.1111/j.1432-1033.1992.tb17060.x. [DOI] [PubMed] [Google Scholar]
  12. Debant A., Guerre-Millo M., Le Marchand-Brustel Y., Freychet P., Lavau M., Van Obberghen E. Insulin receptor kinase is hyperresponsive in adipocytes of young obese Zucker rats. Am J Physiol. 1987 Feb;252(2 Pt 1):E273–E278. doi: 10.1152/ajpendo.1987.252.2.E273. [DOI] [PubMed] [Google Scholar]
  13. Del Prato S., Bonadonna R. C., Bonora E., Gulli G., Solini A., Shank M., DeFronzo R. A. Characterization of cellular defects of insulin action in type 2 (non-insulin-dependent) diabetes mellitus. J Clin Invest. 1993 Feb;91(2):484–494. doi: 10.1172/JCI116226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Denyer G. S., Cooney G. J., Storlien L. H., Jenkins A. B., Kraegen E. W., Kusunoki M., Caterson I. D. Heterogeneity of response to exercise of rat muscle pyruvate dehydrogenase complex. Pflugers Arch. 1991 Sep;419(2):115–120. doi: 10.1007/BF00372995. [DOI] [PubMed] [Google Scholar]
  15. Denyer G. S., Lam D., Cooney G. J., Caterson I. D. Effect of starvation and insulin in vivo on the activity of the pyruvate dehydrogenase complex in rat skeletal muscles. FEBS Lett. 1989 Jul 3;250(2):464–468. doi: 10.1016/0014-5793(89)80777-x. [DOI] [PubMed] [Google Scholar]
  16. Dinneen S., Gerich J., Rizza R. Carbohydrate metabolism in non-insulin-dependent diabetes mellitus. N Engl J Med. 1992 Sep 3;327(10):707–713. doi: 10.1056/NEJM199209033271007. [DOI] [PubMed] [Google Scholar]
  17. Felber J. P., Ferrannini E., Golay A., Meyer H. U., Theibaud D., Curchod B., Maeder E., Jequier E., DeFronzo R. A. Role of lipid oxidation in pathogenesis of insulin resistance of obesity and type II diabetes. Diabetes. 1987 Nov;36(11):1341–1350. doi: 10.2337/diab.36.11.1341. [DOI] [PubMed] [Google Scholar]
  18. Henry R. R., Thorburn A. W., Beerdsen P., Gumbiner B. Dose-response characteristics of impaired glucose oxidation in non-insulin-dependent diabetes mellitus. Am J Physiol. 1991 Jul;261(1 Pt 1):E132–E140. doi: 10.1152/ajpendo.1991.261.1.E132. [DOI] [PubMed] [Google Scholar]
  19. Holness M. J., MacLennan P. A., Palmer T. N., Sugden M. C. The disposition of carbohydrate between glycogenesis, lipogenesis and oxidation in liver during the starved-to-fed transition. Biochem J. 1988 Jun 1;252(2):325–330. doi: 10.1042/bj2520325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kelley D. E., Mokan M., Simoneau J. A., Mandarino L. J. Interaction between glucose and free fatty acid metabolism in human skeletal muscle. J Clin Invest. 1993 Jul;92(1):91–98. doi: 10.1172/JCI116603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kelley D., Mitrakou A., Marsh H., Schwenk F., Benn J., Sonnenberg G., Arcangeli M., Aoki T., Sorensen J., Berger M. Skeletal muscle glycolysis, oxidation, and storage of an oral glucose load. J Clin Invest. 1988 May;81(5):1563–1571. doi: 10.1172/JCI113489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kerbey A. L., Randle P. J., Cooper R. H., Whitehouse S., Pask H. T., Denton R. M. Regulation of pyruvate dehydrogenase in rat heart. Mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: role of coenzyme A, acetyl-coenzyme A and reduced and oxidized nicotinamide-adenine dinucleotide. Biochem J. 1976 Feb 15;154(2):327–348. doi: 10.1042/bj1540327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Krief S., Bazin R., Dupuy F., Lavau M. Increased in vivo glucose utilization in 30-day-old obese Zucker rat: role of white adipose tissue. Am J Physiol. 1988 Mar;254(3 Pt 1):E342–E348. doi: 10.1152/ajpendo.1988.254.3.E342. [DOI] [PubMed] [Google Scholar]
  24. Le Marchand-Brustel Y., Grémeaux T., Ballotti R., Van Obberghen E. Insulin receptor tyrosine kinase is defective in skeletal muscle of insulin-resistant obese mice. Nature. 1985 Jun 20;315(6021):676–679. doi: 10.1038/315676a0. [DOI] [PubMed] [Google Scholar]
  25. Le Marchand Y., Freychet P., Jeanrenaud B. Longitudinal study on the establishment of insulin resistance in hypothalamic obese mice. Endocrinology. 1978 Jan;102(1):74–85. doi: 10.1210/endo-102-1-74. [DOI] [PubMed] [Google Scholar]
  26. Mandarino L. J., Consoli A., Kelley D. E., Reilly J. J., Nurjhan N. Fasting hyperglycemia normalizes oxidative and nonoxidative pathways of insulin-stimulated glucose metabolism in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1990 Dec;71(6):1544–1551. doi: 10.1210/jcem-71-6-1544. [DOI] [PubMed] [Google Scholar]
  27. Mercer S. W., Trayhurn P. Developmental changes in fatty acid synthesis in interscapular brown adipose tissue of lean and genetically obese (ob/ob) mice. Biochem J. 1983 May 15;212(2):393–398. doi: 10.1042/bj2120393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pénicaud L., Ferré P., Terretaz J., Kinebanyan M. F., Leturque A., Doré E., Girard J., Jeanrenaud B., Picon L. Development of obesity in Zucker rats. Early insulin resistance in muscles but normal sensitivity in white adipose tissue. Diabetes. 1987 May;36(5):626–631. doi: 10.2337/diab.36.5.626. [DOI] [PubMed] [Google Scholar]
  29. Pénicaud L., Kinebanyan M. F., Ferré P., Morin J., Kandé J., Smadja C., Marfaing-Jallat P., Picon L. Development of VMH obesity: in vivo insulin secretion and tissue insulin sensitivity. Am J Physiol. 1989 Aug;257(2 Pt 1):E255–E260. doi: 10.1152/ajpendo.1989.257.2.E255. [DOI] [PubMed] [Google Scholar]
  30. Pénicaud L., Rohner-Jeanrenaud F., Jeanrenaud B. In vivo metabolic changes as studied longitudinally after ventromedial hypothalamic lesions. Am J Physiol. 1986 Jun;250(6 Pt 1):E662–E668. doi: 10.1152/ajpendo.1986.250.6.E662. [DOI] [PubMed] [Google Scholar]
  31. RANDLE P. J., GARLAND P. B., HALES C. N., NEWSHOLME E. A. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963 Apr 13;1(7285):785–789. doi: 10.1016/s0140-6736(63)91500-9. [DOI] [PubMed] [Google Scholar]
  32. Vaag A., Skött P., Damsbo P., Gall M. A., Richter E. A., Beck-Nielsen H. Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus. J Clin Invest. 1991 Oct;88(4):1282–1290. doi: 10.1172/JCI115432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Zarjevski N., Doyle P., Jeanrenaud B. Muscle insulin resistance may not be a primary etiological factor in the genetically obese fa/fa rat. Endocrinology. 1992 Mar;130(3):1564–1570. doi: 10.1210/endo.130.3.1537306. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES