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. 1992 Sep 1;286(Pt 2):513–517. doi: 10.1042/bj2860513

Mechanisms regulating cardiac fuel selection in hyperthyroidism.

M C Sugden 1, M J Holness 1, Y L Liu 1, D M Smith 1, L G Fryer 1, Y T Kruszynska 1
PMCID: PMC1132927  PMID: 1530584

Abstract

Starvation (48 h) decreases fructose 2,6-bisphosphate (Fru-2,6-P2) concentrations and the ratio of free to acylated carnitine in hearts of euthyroid rats. These decreases, which are indicative of increased lipid fuel oxidation, are accompanied by decreased rates of glucose uptake and phosphorylation, assessed by using radioactive 2-deoxyglucose. Cardiac concentrations of acylated carnitines were increased at the expense of free carnitine even in the fed state in response to experimental hyperthyroidism, but neither Fru-2,6-P2 concentrations nor rates of glucose utilization were suppressed. Starvation (48 h) did not further increase the proportion of acylated carnitine in the heart in hyperthyroidism, and suppression of Fru-2,6-P2 concentrations and glucose utilization rates by starvation was attenuated. Although glucose utilization rates were decreased, starvation did not decrease immunoreactive GLUT 4 protein concentrations. Furthermore, although hyperthyroidism was associated with a statistically significant (30-40%) increase in relative abundance of GLUT 4 mRNA, the amount of GLUT 4 protein was not increased by hyperthyroidism in either the fed or the starved state. The results demonstrate a significant effect of hyperthyroidism to enhance cardiac glucose utilization in starvation by a mechanism which does not involve changes in GLUT 4 expression but may be secondary to changes in glucose-lipid interactions at the tissue level.

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Selected References

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

  1. Bell G. I., Kayano T., Buse J. B., Burant C. F., Takeda J., Lin D., Fukumoto H., Seino S. Molecular biology of mammalian glucose transporters. Diabetes Care. 1990 Mar;13(3):198–208. doi: 10.2337/diacare.13.3.198. [DOI] [PubMed] [Google Scholar]
  2. Birnbaum M. J. Identification of a novel gene encoding an insulin-responsive glucose transporter protein. Cell. 1989 Apr 21;57(2):305–315. doi: 10.1016/0092-8674(89)90968-9. [DOI] [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  4. Casla A., Rovira A., Wells J. A., Dohm G. L. Increased glucose transporter (GLUT4) protein expression in hyperthyroidism. Biochem Biophys Res Commun. 1990 Aug 31;171(1):182–188. doi: 10.1016/0006-291x(90)91374-2. [DOI] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Ferré P., Burnol A. F., Leturque A., Terretaz J., Penicaud L., Jeanrenaud B., Girard J. Glucose utilization in vivo and insulin-sensitivity of rat brown adipose tissue in various physiological and pathological conditions. Biochem J. 1986 Jan 1;233(1):249–252. doi: 10.1042/bj2330249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ferré P., Leturque A., Burnol A. F., Penicaud L., Girard J. A method to quantify glucose utilization in vivo in skeletal muscle and white adipose tissue of the anaesthetized rat. Biochem J. 1985 May 15;228(1):103–110. doi: 10.1042/bj2280103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. French T. J., Goode A. W., Holness M. J., MacLennan P. A., Sugden M. C. The relationship between changes in lipid fuel availability and tissue fructose 2,6-bisphosphate concentrations and pyruvate dehydrogenase complex activities in the fed state. Biochem J. 1988 Dec 15;256(3):935–939. doi: 10.1042/bj2560935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. French T. J., Holness M. J., MacLennan P. A., Sugden M. C. Effects of nutritional status and acute variation in substrate supply on cardiac and skeletal-muscle fructose 2,6-bisphosphate concentrations. Biochem J. 1988 Mar 15;250(3):773–779. doi: 10.1042/bj2500773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Garber D. W., Everett A. W., Neely J. R. Cardiac function and myosin ATPase in diabetic rats treated with insulin, T3, and T4. Am J Physiol. 1983 Apr;244(4):H592–H598. doi: 10.1152/ajpheart.1983.244.4.H592. [DOI] [PubMed] [Google Scholar]
  11. Gustafson T. A., Markham B. E., Morkin E. Effects of thyroid hormone on alpha-actin and myosin heavy chain gene expression in cardiac and skeletal muscles of the rat: measurement of mRNA content using synthetic oligonucleotide probes. Circ Res. 1986 Aug;59(2):194–201. doi: 10.1161/01.res.59.2.194. [DOI] [PubMed] [Google Scholar]
  12. Henriksen E. J., Bourey R. E., Rodnick K. J., Koranyi L., Permutt M. A., Holloszy J. O. Glucose transporter protein content and glucose transport capacity in rat skeletal muscles. Am J Physiol. 1990 Oct;259(4 Pt 1):E593–E598. doi: 10.1152/ajpendo.1990.259.4.E593. [DOI] [PubMed] [Google Scholar]
  13. Holness M. J., French T. J., Schofield P. S., Sugden M. C. The relationship between fat synthesis and oxidation in the liver after re-feeding and its regulation by thyroid hormone. Biochem J. 1987 Nov 1;247(3):621–626. doi: 10.1042/bj2470621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Holness M. J., Palmer T. N., Sugden M. C. Effects of administration of tri-iodothyronine on the response of cardiac and renal pyruvate dehydrogenase complex to starvation for 48 h. Biochem J. 1985 Nov 15;232(1):255–259. doi: 10.1042/bj2320255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Holness M. J., Sugden M. C. Glucose disposal by skeletal muscle in response to re-feeding after progressive starvation. Biochem J. 1991 Jul 15;277(Pt 2):429–433. doi: 10.1042/bj2770429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Holness M. J., Sugden M. C. Glucose utilization in heart, diaphragm and skeletal muscle during the fed-to-starved transition. Biochem J. 1990 Aug 15;270(1):245–249. doi: 10.1042/bj2700245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Huang M. T., Lardy H. A. Effects of thyroid states on the Cori cycle, glucose--alanine cycle, and futile cycling of glucose metabolism in rats. Arch Biochem Biophys. 1981 Jun;209(1):41–51. doi: 10.1016/0003-9861(81)90254-x. [DOI] [PubMed] [Google Scholar]
  19. Hue L., Maisin L., Rider M. H. Palmitate inhibits liver glycolysis. Involvement of fructose 2,6-bisphosphate in the glucose/fatty acid cycle. Biochem J. 1988 Apr 15;251(2):541–545. doi: 10.1042/bj2510541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Issad T., Pénicaud L., Ferré P., Kandé J., Baudon M. A., Girard J. Effects of fasting on tissue glucose utilization in conscious resting rats. Major glucose-sparing effect in working muscles. Biochem J. 1987 Aug 15;246(1):241–244. doi: 10.1042/bj2460241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. James D. E., Burleigh K. M., Chisholm D. J., Kraegen E. W. In vivo dose response curves of insulin action in heart: anomalous effects at high insulin doses. J Mol Cell Cardiol. 1985 Oct;17(10):981–985. doi: 10.1016/s0022-2828(85)80078-x. [DOI] [PubMed] [Google Scholar]
  22. James D. E., Kraegen E. W., Chisholm D. J. Muscle glucose metabolism in exercising rats: comparison with insulin stimulation. Am J Physiol. 1985 May;248(5 Pt 1):E575–E580. doi: 10.1152/ajpendo.1985.248.5.E575. [DOI] [PubMed] [Google Scholar]
  23. James D. E., Strube M., Mueckler M. Molecular cloning and characterization of an insulin-regulatable glucose transporter. Nature. 1989 Mar 2;338(6210):83–87. doi: 10.1038/338083a0. [DOI] [PubMed] [Google Scholar]
  24. Kahn B. B., Flier J. S. Regulation of glucose-transporter gene expression in vitro and in vivo. Diabetes Care. 1990 Jun;13(6):548–564. doi: 10.2337/diacare.13.6.548. [DOI] [PubMed] [Google Scholar]
  25. Klip A., Ramlal T., Young D. A., Holloszy J. O. Insulin-induced translocation of glucose transporters in rat hindlimb muscles. FEBS Lett. 1987 Nov 16;224(1):224–230. doi: 10.1016/0014-5793(87)80452-0. [DOI] [PubMed] [Google Scholar]
  26. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  27. Lawson J. W., Uyeda K. Effects of insulin and work on fructose 2,6-bisphosphate content and phosphofructokinase activity in perfused rat hearts. J Biol Chem. 1987 Mar 5;262(7):3165–3173. [PubMed] [Google Scholar]
  28. Okajima F., Ui M. Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Glucose-turnover values and futile-cycle activities obtained with 14C- and 3H-labelled glucose. Biochem J. 1979 Aug 15;182(2):565–575. doi: 10.1042/bj1820565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Okajima F., Ui M. Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Minor role of endogenous insulin in thyroid-dependent changes in glucose turnover. Biochem J. 1979 Aug 15;182(2):577–584. doi: 10.1042/bj1820577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pearson D. J., Tubbs P. K. Carnitine and derivatives in rat tissues. Biochem J. 1967 Dec;105(3):953–963. doi: 10.1042/bj1050953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pedersen O., Bak J. F., Andersen P. H., Lund S., Moller D. E., Flier J. S., Kahn B. B. Evidence against altered expression of GLUT1 or GLUT4 in skeletal muscle of patients with obesity or NIDDM. Diabetes. 1990 Jul;39(7):865–870. doi: 10.2337/diab.39.7.865. [DOI] [PubMed] [Google Scholar]
  32. Pénicaud L., Ferré P., Kande J., Leturque A., Issad T., Girard J. Effect of anesthesia on glucose production and utilization in rats. Am J Physiol. 1987 Mar;252(3 Pt 1):E365–E369. doi: 10.1152/ajpendo.1987.252.3.E365. [DOI] [PubMed] [Google Scholar]
  33. Randle P. J., Newsholme E. A., Garland P. B. Regulation of glucose uptake by muscle. 8. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes and starvation, on the uptake and metabolic fate of glucose in rat heart and diaphragm muscles. Biochem J. 1964 Dec;93(3):652–665. doi: 10.1042/bj0930652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Richards C. S., Uyeda K. Changes in the concentration of activation factor for phosphofructokinase in hepatocytes in response to glucose and glucagon. Biochem Biophys Res Commun. 1980 Dec 31;97(4):1535–1540. doi: 10.1016/s0006-291x(80)80040-4. [DOI] [PubMed] [Google Scholar]
  35. Roychoudhury R., Wu R. Terminal transferase-catalyzed addition of nucleotides to the 3' termini of DNA. Methods Enzymol. 1980;65(1):43–62. doi: 10.1016/s0076-6879(80)65009-5. [DOI] [PubMed] [Google Scholar]
  36. Schofield P. S., French T. J., Goode A. W., Sugden M. C. Liver carnitine metabolism after partial hepatectomy in the rat. Effects of nutritional status and inhibition of carnitine palmitoyltransferase. FEBS Lett. 1985 May 20;184(2):214–220. doi: 10.1016/0014-5793(85)80609-8. [DOI] [PubMed] [Google Scholar]
  37. Sugden M. C., Liu Y. L., Holness M. J. Glucose utilization and disposal in cardiothoracic and skeletal muscles during the starved-to-fed transition in the rat. Biochem J. 1990 Nov 15;272(1):133–137. doi: 10.1042/bj2720133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sugden M. C., Liu Y. L., Holness M. J. Glucose utilization by skeletal muscles in vivo in experimental hyperthyroidism in the rat. Biochem J. 1990 Oct 15;271(2):421–425. doi: 10.1042/bj2710421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wake S. A., Sowden J. A., Storlien L. H., James D. E., Clark P. W., Shine J., Chisholm D. J., Kraegen E. W. Effects of exercise training and dietary manipulation on insulin-regulatable glucose-transporter mRNA in rat muscle. Diabetes. 1991 Feb;40(2):275–279. doi: 10.2337/diab.40.2.275. [DOI] [PubMed] [Google Scholar]
  40. Weinstein S. P., Watts J., Haber R. S. Thyroid hormone increases muscle/fat glucose transporter gene expression in rat skeletal muscle. Endocrinology. 1991 Jul;129(1):455–464. doi: 10.1210/endo-129-1-455. [DOI] [PubMed] [Google Scholar]

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