Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase. Evidence for their role in oxidative and nonoxidative glucose metabolism (original) (raw)

Abstract

To determine whether activation by insulin of glycogen synthase (GS), phosphofructokinase (PFK), or pyruvate dehydrogenase (PDH) in skeletal muscle regulates intracellular glucose metabolism, subjects were studied basally and during euglycemic insulin infusions of 12, 30, and 240 mU/m2 X min. Glucose disposal, oxidative and nonoxidative glucose metabolism were determined. GS, PFK, and PDH were assayed in skeletal muscle under each condition. Glucose disposal rates were 2.37 +/- 0.11, 3.15 +/- 0.19, 6.71 +/- 0.44, and 11.7 +/- 1.73 mg/kg X min; glucose oxidation rates were 1.96 +/- 0.18, 2.81 +/- 0.28, 4.43 +/- 0.32, and 5.22 +/- 0.52. Nonoxidative glucose metabolism was 0.39 +/- 0.13, 0.34 +/- 0.26, 2.28 +/- 0.40, and 6.52 +/- 1.21 mg/kg X min. Both the proportion of active GS and the proportion of active PDH were increased by hyperinsulinemia. PFK activity was unaffected. Activation of GS was correlated with nonoxidative glucose metabolism, while activation of PDH was correlated with glucose oxidation. Sensitivity to insulin of GS was similar to that of nonoxidative glucose metabolism, while the sensitivity to insulin of PDH was similar to that of glucose oxidation. Therefore, the activation of these enzymes in muscle may regulate nonoxidative and oxidative glucose metabolism.

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Selected References

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  1. Baron A. D., Kolterman O. G., Bell J., Mandarino L. J., Olefsky J. M. Rates of noninsulin-mediated glucose uptake are elevated in type II diabetic subjects. J Clin Invest. 1985 Nov;76(5):1782–1788. doi: 10.1172/JCI112169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blass J. P., Avigan J., Uhlendorf B. W. A defect in pyruvate decarboxylase in a child with an intermittent movement disorder. J Clin Invest. 1970 Mar;49(3):423–432. doi: 10.1172/JCI106251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boden G., Ray T. K., Smith R. H., Owen O. E. Carbohydrate oxidation and storage in obese non-insulin-dependent diabetic patients. Effects of improving glycemic control. Diabetes. 1983 Nov;32(11):982–987. doi: 10.2337/diab.32.11.982. [DOI] [PubMed] [Google Scholar]
  4. Bogardus C., Lillioja S., Stone K., Mott D. Correlation between muscle glycogen synthase activity and in vivo insulin action in man. J Clin Invest. 1984 Apr;73(4):1185–1190. doi: 10.1172/JCI111304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bolinder J., Ostman J., Arner P. Postreceptor defects causing insulin resistance in normoinsulinemic non-insulin-dependent diabetes mellitus. Diabetes. 1982 Oct;31(10):911–916. doi: 10.2337/diab.31.10.911. [DOI] [PubMed] [Google Scholar]
  6. Ciaraldi T. P., Kolterman O. G., Scarlett J. A., Kao M., Olefsky J. M. Role of glucose transport in the postreceptor defect of non-insulin-dependent diabetes mellitus. Diabetes. 1982 Nov;31(11):1016–1022. doi: 10.2337/diacare.31.11.1016. [DOI] [PubMed] [Google Scholar]
  7. DeFronzo R. A., Jacot E., Jequier E., Maeder E., Wahren J., Felber J. P. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes. 1981 Dec;30(12):1000–1007. doi: 10.2337/diab.30.12.1000. [DOI] [PubMed] [Google Scholar]
  8. Denton R. M., Randle P. J., Bridges B. J., Cooper R. H., Kerbey A. L., Pask H. T., Severson D. L., Stansbie D., Whitehouse S. Regulation of mammalian pyruvate dehydrogenase. Mol Cell Biochem. 1975 Oct 31;9(1):27–53. doi: 10.1007/BF01731731. [DOI] [PubMed] [Google Scholar]
  9. Devlin J. T., Horton E. S. Effects of prior high-intensity exercise on glucose metabolism in normal and insulin-resistant men. Diabetes. 1985 Oct;34(10):973–979. doi: 10.2337/diab.34.10.973. [DOI] [PubMed] [Google Scholar]
  10. Evans D. J., Murray R., Kissebah A. H. Relationship between skeletal muscle insulin resistance, insulin-mediated glucose disposal, and insulin binding. Effects of obesity and body fat topography. J Clin Invest. 1984 Oct;74(4):1515–1525. doi: 10.1172/JCI111565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. FRIEDMAN D. L., LARNER J. STUDIES ON UDPG-ALPHA-GLUCAN TRANSGLUCOSYLASE. III. INTERCONVERSION OF TWO FORMS OF MUSCLE UDPG-ALPHA-GLUCAN TRANSGLUCOSYLASE BY A PHOSPHORYLATION-DEPHOSPHORYLATION REACTION SEQUENCE. Biochemistry. 1963 Jul-Aug;2:669–675. doi: 10.1021/bi00904a009. [DOI] [PubMed] [Google Scholar]
  12. Felber J. P., Thiébaud D., Maeder E., Jéquier E., Hendler R., DeFronzo R. A. Effect of somatostatin-induced insulinopenia on glucose oxidation in man. Diabetologia. 1983 Oct;25(4):325–330. doi: 10.1007/BF00253195. [DOI] [PubMed] [Google Scholar]
  13. Frayn K. N. Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol Respir Environ Exerc Physiol. 1983 Aug;55(2):628–634. doi: 10.1152/jappl.1983.55.2.628. [DOI] [PubMed] [Google Scholar]
  14. Garland P. B., Newsholme E. A., Randle P. J. Regulation of glucose uptake by muscle. 9. Effects of fatty acids and ketone bodies, and of alloxan-diabetes and starvation, on pyruvate metabolism and on lactate-pyruvate and L-glycerol 3-phosphate-dihydroxyacetone phosphate concentration ratios in rat heart and rat diaphragm muscles. Biochem J. 1964 Dec;93(3):665–678. doi: 10.1042/bj0930665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Garland P. B., Randle P. J. Regulation of glucose uptake by muscles. 10. Effects of alloxan-diabetes, starvation, hypophysectomy and adrenalectomy, and of fatty acids, ketone bodies and pyruvate, on the glycerol output and concentrations of free fatty acids, long-chain fatty acyl-coenzyme A, glycerol phosphate and citrate-cycle intermediates in rat heart and diaphragm muscles. Biochem J. 1964 Dec;93(3):678–687. doi: 10.1042/bj0930678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gottesman I., Mandarino L., Verdonk C., Rizza R., Gerich J. Insulin increases the maximum velocity for glucose uptake without altering the Michaelis constant in man. Evidence that insulin increases glucose uptake merely by providing additional transport sites. J Clin Invest. 1982 Dec;70(6):1310–1314. doi: 10.1172/JCI110731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hagg S. A., Taylor S. I., Ruberman N. B. Glucose metabolism in perfused skeletal muscle. Pyruvate dehydrogenase activity in starvation, diabetes and exercise. Biochem J. 1976 Aug 15;158(2):203–210. doi: 10.1042/bj1580203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. ITAYA K., UI M. COLORIMETRIC DETERMINATION OF FREE FATTY ACIDS IN BIOLOGICAL FLUIDS. J Lipid Res. 1965 Jan;6:16–20. [PubMed] [Google Scholar]
  19. Kaslow H. R., Eichner R. D. Fasting and diabetes alter adipose tissue glycogen synthase. Am J Physiol. 1984 Nov;247(5 Pt 1):E581–E584. doi: 10.1152/ajpendo.1984.247.5.E581. [DOI] [PubMed] [Google Scholar]
  20. Kochan R. G., Lamb D. R., Lutz S. A., Perrill C. V., Reimann E. M., Schlender K. K. Glycogen synthase activation in human skeletal muscle: effects of diet and exercise. Am J Physiol. 1979 Jun;236(6):E660–E666. doi: 10.1152/ajpendo.1979.236.6.E660. [DOI] [PubMed] [Google Scholar]
  21. Kochan R. G., Lamb D. R., Reimann E. M., Schlender K. K. Modified assays to detect activation of glycogen synthase following exercise. Am J Physiol. 1981 Feb;240(2):E197–E202. doi: 10.1152/ajpendo.1981.240.2.E197. [DOI] [PubMed] [Google Scholar]
  22. Kolterman O. G., Gray R. S., Griffin J., Burstein P., Insel J., Scarlett J. A., Olefsky J. M. Receptor and postreceptor defects contribute to the insulin resistance in noninsulin-dependent diabetes mellitus. J Clin Invest. 1981 Oct;68(4):957–969. doi: 10.1172/JCI110350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kolterman O. G., Insel J., Saekow M., Olefsky J. M. Mechanisms of insulin resistance in human obesity: evidence for receptor and postreceptor defects. J Clin Invest. 1980 Jun;65(6):1272–1284. doi: 10.1172/JCI109790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  25. Lönnroth P., Digirolamo M., Krotkiewski M., Smith U. Insulin binding and responsiveness in fat cells from patients with reduced glucose tolerance and type II diabetes. Diabetes. 1983 Aug;32(8):748–754. doi: 10.2337/diab.32.8.748. [DOI] [PubMed] [Google Scholar]
  26. Mandarino L. J., Madar Z., Kolterman O. G., Bell J. M., Olefsky J. M. Adipocyte glycogen synthase and pyruvate dehydrogenase in obese and type II diabetic subjects. Am J Physiol. 1986 Oct;251(4 Pt 1):E489–E496. doi: 10.1152/ajpendo.1986.251.4.E489. [DOI] [PubMed] [Google Scholar]
  27. Nuttall F. Q., Barbosa J., Gannon M. C. The glycogen synthase system in skeletal muscle of normal humans and patients with myotonic dystrophy: effect of glucose and insulin administration. Metabolism. 1974 Jun;23(6):561–568. doi: 10.1016/0026-0495(74)90084-5. [DOI] [PubMed] [Google Scholar]
  28. Pedersen O., Hjøllund E., Sørensen N. S. Insulin receptor binding and insulin action in human fat cells: effects of obesity and fasting. Metabolism. 1982 Sep;31(9):884–895. doi: 10.1016/0026-0495(82)90177-9. [DOI] [PubMed] [Google Scholar]
  29. ROSELL-PEREZ M., VILLAR-PALASI C., LARNER J. Studies on UDPG-glycogen transglucosylase. I. Preparation and differentiation of two activities of UDPG-glycogen transglucosylase from rat skeletal muscle. Biochemistry. 1962 Sep;1:763–768. doi: 10.1021/bi00911a005. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Roch-Norlund A. E., Bergström J., Hultman E. Muscle glycogen and glycogen synthetase in normal subjects and in patients with diabetes mellitus. Effect of intravenous glucose and insulin administration. Scand J Clin Lab Invest. 1972 Sep;30(1):77–84. doi: 10.3109/00365517209081094. [DOI] [PubMed] [Google Scholar]
  32. STEELE R., WALL J. S., DE BODO R. C., ALTSZULER N. Measurement of size and turnover rate of body glucose pool by the isotope dilution method. Am J Physiol. 1956 Sep;187(1):15–24. doi: 10.1152/ajplegacy.1956.187.1.15. [DOI] [PubMed] [Google Scholar]
  33. Thiebaud D., Jacot E., DeFronzo R. A., Maeder E., Jequier E., Felber J. P. The effect of graded doses of insulin on total glucose uptake, glucose oxidation, and glucose storage in man. Diabetes. 1982 Nov;31(11):957–963. doi: 10.2337/diacare.31.11.957. [DOI] [PubMed] [Google Scholar]
  34. Thomas J. A., Schlender K. K., Larner J. A rapid filter paper assay for UDPglucose-glycogen glucosyltransferase, including an improved biosynthesis of UDP-14C-glucose. Anal Biochem. 1968 Oct 24;25(1):486–499. doi: 10.1016/0003-2697(68)90127-9. [DOI] [PubMed] [Google Scholar]
  35. Weiss L., Löffler G., Schirmann A., Wieland O. Control of pyruvate dehydrogenase interconversion in adipose tissue by insulin. FEBS Lett. 1971 Jun 24;15(3):229–231. doi: 10.1016/0014-5793(71)80318-6. [DOI] [PubMed] [Google Scholar]