Skip to main content
SpringerLink
Log in

Insulin-status-dependent modulation of FoF1-ATPase activity in rat liver mitochondria

  • Articles
  • Published:
Lipids

Abstract

Early and late effects of alloxan diabetes and insulin treatment on mitochondrial membrane structure and function were evaluated by studying the kinetic properties of mitochondrial membrane marker enzyme FoF1-ATPase and its modulation by membrane lipid/phospholipid composition and membrane fluidity. Under all experimental conditions the enzyme displayed three kinetically distinguishable components. In 1wk-old diabetic animals the enzyme activity was unchanged; however, K m and V max of component I increased and K m of component II decreased. Insulin treatment resulted in lowering of K m and V max of components II and III. One-mon diabetic state resulted in decreased enzyme activity, whereas insulin treatment caused hyperstimulation. K m of components I and II decreased together with decreased V max of all the components. Insulin treatment restored the K m and V max values. In late-stage diabetes the catalytic efficiency of components I and II increased; insulin treatment had drastic adverse effect. Binding pattern of ATP was unchanged under all experimental conditions. Diabetic state resulted in progressive decrease in energy of activation in the low temperature range (E L). Insulin treatment lowered the energy of activation in the high temperature range (E H) without correcting the E L values. The phase transition temperatures increased in diabetic state and were not corrected by insulin treatment. Long-term diabetes lowered the total phospholipid content and elevated the cholesterol content; insulin treatment had partial restorative effect. The membrane fluidity decreased in general in diabetic condition and was not corrected by insulin treatment at late stage. Regression analysis studies suggest that specific phospholipid classes and/or their ratios may play a role in modulation of the enzyme activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CHL:

cholesterol

DPG:

diphosphatidyl glycerol

Lyso:

lysophospholipid

PI:

phosphatidylinositol

PLTP:

plasma phospholipid transport protein

PS:

phosphatidylserine

s.c.:

subcutaneously

SPM:

sphingomylein

TPL:

total phospholipid

References

  1. Alberti, K.G.M.M., and Press, C.M. (1982) The Biochemistry of the Complications of Diabetes Mellitus, in: M. Keen, J. Jarrett, (Eds.), Complications of Diabetes. Edward Arnold Ltd., London, pp. 231–270.

    Google Scholar 

  2. Mohan, C., Geiger, P. J., and Bessman, S. P. (1989) The Intracellular Site of Action of Insulin: The Mitochondrial Krebs Cycle, Curr. Topics Cell. Reg. 30, 105–142.

    CAS  Google Scholar 

  3. Singleton, J.R., Smith, A.G., Russel, J.W., and Feldman, E.L. (2003) Microvascular Complication of Impaired Glucose Tolerance, Diabetes 52, 2867–2873.

    PubMed  CAS  Google Scholar 

  4. Ceriello, A. (2005) Postprandial Hyperglycemia and Diabetes Complications. Is It Time to Treat?. Diabetes 54, 1–7.

    PubMed  CAS  Google Scholar 

  5. Rodriguez, Y., and Christophe, A.B. (2004) Effect of Diabetes Mellitus and Different Treatments on Plasma and Erythrocyte Phospholipid Fatty Acid Composition in Type 2 Diabetics, Ann. Nutr. Metab. 48, 335–342.

    Article  PubMed  CAS  Google Scholar 

  6. Schneider, M., Verges, B., Klein, A., Miller, E.R., Deckert, V., Desrumaux, C., Masson, D., Gambert, P., Brun, J.M., Fruchart-Najib, J., Blache, D., Witztum, J.L., and Lagrost, L. (2004) Alterations in Plasma Vitamin E Distribution in Type 2 Diabetic Patients with Elevated Plasma Phospholipid Transfer Protein Activity, Diabetes 53, 2633–2639.

    PubMed  CAS  Google Scholar 

  7. Oomen, P.H., van Tol, A., Hattori, H., Smit, A.J., Scheek, L.M., and Dullaart, R.P. (2005) Human Plasma Phospholipid Transfer Protein Activity Is Decreased by Acute Hyperglycaemia: Studies Without and with Hyperinsulinaemia in Type 1 Diabetes Mellitus, Diabet. Med. 22, 768–774.

    Article  PubMed  CAS  Google Scholar 

  8. Dullaart, R.P., de Vries, R., Scheek, L., Borggreve, S.E., van Gent, T., Dallinga-Thie, G.M., Ito, M., Nagano, M., Sluiter, W.J., Hattori, H., and van Tol, A. (2004) Type 2 Diabetes Mellitus Is Associated with Differential Effects on Plasma Cholesteryl Ester Transfer Protein and Phospholipid Transfer Protein Activities and Concentrations, Scand. J. Clin. Lab. Invest. 64, 205–215.

    Article  PubMed  CAS  Google Scholar 

  9. He, J., Qiu, Y., Yan, Y., and Niu, Y. (1998) Relationship Between Changes of Phospholipid and Lipid Peroxide of Erythrocyte Membrane and Diabetic Retinopathy, Zhonghua. Yan. Ke. Za. Zhi. 34, 202–204

    PubMed  CAS  Google Scholar 

  10. Sailaja, Y.R., Baskar, R., Rao, C.S.S., and Saralakumari, D. (2004) Membrane Lipids and Protein-Bound Carbohydrates Status During the Maturation of Reticulocytes to Erythrocytes in Type 2 Diabetics. Clin. Chim. Acta 341, 185–192.

    Article  PubMed  CAS  Google Scholar 

  11. Dave, K.R. Biochemical Investigations on Cardiovascular Functions in Diabetes, Ph.D. Thesis, The Maharaja Sayajirao University of Baroda, 1999.

  12. Kuwahara, Y., Yanagishita, T., Konno, N., and Katagiri, T. (1997) Changes in Microsomal Membrane Phospholipids and Fatty Acids and in Activities of Membrane-Bound Enzyme in Diabetic Rat Heart, Basic Res. Cardiol. 92, 214–222.

    Article  PubMed  CAS  Google Scholar 

  13. Brenner, R.R., Bernasconi, A.M., and Garda, H.A. (2000) Effect of Experimental Diabetes on the Fatty Acid Composition, Molecular Species of Phosphatidyl Choline and Physical Properties of Hepatic Microsomal Membranes. Prostaglandins Leukot. Essent. Fatty Acids. 63, 167–176.

    Article  PubMed  CAS  Google Scholar 

  14. Coste, T., Pierlovisi, M., Leonardi, J., Dufayet, D., Gerbi, A., Lafont, H., Vague, P., and Raccah, D. (1999) Beneficial Effects of Gamma Linolenic Acid Supplementation on Nerve Conduction Velocity, Na+, K+-ATPase Activity, and Membrane Fatty Acid Composition in Sciatic Nerve of Diabetic Rats. J. Nutr. Biochem. 10, 411–420.

    Article  PubMed  CAS  Google Scholar 

  15. Rabini, R.A., Fumelli, P., Zolese, G., Amler, E., Salyolini, E., Staffolani, R., Cester, N., and Mazzanti, L. (1998) Modifications Induced by Plasma from Insulin-Dependent Diabetic Patients and by Lysophosphatidylcholine on Human Na+, K(+)-Adenosine triphosphatase, J. Clin. Endocrinol. Metab. 83, 2405–2410.

    Article  PubMed  CAS  Google Scholar 

  16. Satav, J.G., and Katyare, S.S. (2004) Effect of Streptozotocin-Induced Diabetes on Oxidative Energy Metabolism in Rat Liver Mitochondria—A Comparative Study of Early and Late Effects. Ind. J. Clin. Biochem. 19, 26–36.

    Article  Google Scholar 

  17. Brignone, J.A., de Brignone, C.M.C., Rodriguez, R.R., Badano, B.M., and Stoppani, A.O.M. (1982) Modified Oscillation Behavior and Decreased d-3-Hydroxybutyrate Dehydrogenase Activity in Diabetic Rat Liver Mitochondria, Arch. Biochem. Biophys. 214, 581–588.

    Article  PubMed  CAS  Google Scholar 

  18. Ferreira, F.M., Seica, R., Oliveira, P.J., Coxito, P.M., Moreno, A.J., Palmeira, C.M., and Santos, M.S. (2003) Diabetes Induces Metabolic Adaptations in Rat Liver Mitochondria: Role of Coenzyme Q and Cardiolipin Contents. Biochim. Biophys. Acta, 1639, 113–120.

    PubMed  CAS  Google Scholar 

  19. Syroeshkin, A.V., Vasilyeva, E.A., and Vinogradov, A.D. (1995) ATP Synthesis Catalyzed by the Mitochondrial F1−F0 ATP Synthase Is Not a Reversal of Its ATPase Activity, FEBS Lett. 366, 29–32.

    Article  PubMed  CAS  Google Scholar 

  20. Noji, H., and Yoshida, M. (2001) The Rotary Machine in the Cell, ATP Synthase, J. Biol. Chem. 276, 1665–1668.

    Article  PubMed  CAS  Google Scholar 

  21. Daum, G. (1985) Lipids of Mitochondria, Biochim. Biophys. Acta, 822, 1–42.

    PubMed  CAS  Google Scholar 

  22. Satav, J.G., Dave, K.R., and Katyare, S.S. (2000) Influence of Insulin Status on Extra-mitochondrial Oxygen Metabolism in the Rat. Horm. Metab. Res. 32, 57–61.

    Article  PubMed  CAS  Google Scholar 

  23. Dave, K.R., and Katyare, S.S. (2002) Effect of Alloxan-Induced Diabetes on Serum and Cardiac Butyrylcholinesterase in the Rat, J. Endocrinal. 175, 241–250.

    Article  CAS  Google Scholar 

  24. Park, C., and Drake, R.L. (1982) Insulin Mediates the Stimulation of Pyruvate Kinase by a Dual Mechanism, Biochem. J. 208, 333–337.

    Google Scholar 

  25. Katewa, S.D., and Katyare, S.S. (2004) Treatment with Antimalarials Adversely Affects the Oxidative Energy Metabolism in Rat Liver Mitochondria. Drug Chem. Toxicol. 27, 41–53.

    Article  PubMed  CAS  Google Scholar 

  26. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. (1951) Protein Measurement with the Folin Phenol Reagent, J. Biol. Chem. 193, 265–275.

    PubMed  CAS  Google Scholar 

  27. Skipski, V.P., Barclay, M., Barclay, R.K., Fetzer, V.A., Good, J.J., and Archibald, F.M. (1967) Lipid Composition of Human Serum Lipoprotein, Biochem. J. 104, 340–361.

    PubMed  CAS  Google Scholar 

  28. Zlatkis, A., Zak, B., and Boyle, A.J. (1953) A New Method for the Determination of Serum Cholesterol, J. Lab. Clin. Med. 41, 486–492.

    PubMed  CAS  Google Scholar 

  29. Bartlett, G.R. (1954) Phosphorus Assay in Column Chromatography. J. Biol. Chem. 234, 466–468.

    Google Scholar 

  30. Pandya, J.D., Dave, K.R., and Katyare, S.S. (2001) Effect of Long-Term Aluminum Feeding on Lipid/Phospholipid Profiles of Rat Brain Synaptic Plasma Membranes and Microsomes. J. Alzheimer's Dis. 3, 531–539.

    CAS  Google Scholar 

  31. Katyare, S.S., Joshi, M.V., Fatterpaker, P., and Sreenivasan A. (1977) Effect of Thyroid Deficiency on Oxidative Phosphorylation in Rat Liver, Kidney and Brain Mitochondria, Arch. Biochem. Biophys. 182, 155–163.

    Article  PubMed  CAS  Google Scholar 

  32. Katewa, S.D., and Katyare, S.S. (2003) Simplified Method for Inorganic Phosphate Determination and Its Application for Phosphate Analysis in Enzyme Assays, Anal. Biochem. 323, 180–187.

    Article  PubMed  CAS  Google Scholar 

  33. Dixon, M., and Webb, E.C. (1979) in Enzymes, 3rd edn. Dixon M., Webb E.C., Thorne C. Jr., and Tipton K.F., eds., Longman, London, pp. 332–466.

    Google Scholar 

  34. Mathews, C.K., and van Holde, K.E. (1996) Biochemistry, 2nd edn. The Benjamin Cummings Publishing Co., Menlo Park, CA, pp. 359–414.

    Google Scholar 

  35. Pedersen, P.L., and Amzel, L.M., (1993) ATP Synthase: Structure, Reaction Center, Mechanism, and Regulation of One of Nature's Most Unique Machines, J. Biol. Chem. 268, 9937–9940.

    PubMed  CAS  Google Scholar 

  36. Cerdan, E., Compo, M.L., Lopez-Moratalla, N., and Santiago, E. (1983) Three Catalytic Sites in Mitochondrial ATPase, FEBS Lett. 158, 151–157.

    Article  PubMed  CAS  Google Scholar 

  37. Parmar, D.V., Ahmed, G., Khandkar, M.A., and Katyare, S.S., (1995) Mitochondrial ATPase: A Target for Paracetamol-Induced Hepatotoxicity, Eur. J. Pharmacol. 293, 225–229.

    Article  PubMed  CAS  Google Scholar 

  38. Matschinsky, F.M. (1996) Banting Lecture 1995. A lesson in Metabolic Regulation Impaired by the Glucokinase Glucose Sensor Paradigm, Diabetes 45, 223–241.

    PubMed  CAS  Google Scholar 

  39. Anello, M., Lupi, R., Spampinato, D., Piro, S., Masini, M., Boggi, U., Del Parto, S., Rabuzzao, A.M., Purrello, F., and Marchetti, P. (2005) Functional and Morphological Alterations of Mitochondria in Pancreatic Beta Cell from Type 2 Diabetes Patients, Diabetologia 48, 282–289.

    Article  PubMed  CAS  Google Scholar 

  40. Maassen, J.A., Hart, L.M., van Essen, E., Heine, R.J., Nijpels, G., Tafrechi, R.S.J., Raap, A.K., Janssen, G.M.C., and Lemkes, H.H.P.J. (2004) Mitochondrial Diabetes, Molecular Mechanisms and Clinical Presentation, Diabetes 53, S103-S109.

    PubMed  CAS  Google Scholar 

  41. Ido, Y., Vindigni, A., Chang, K., Shamon, L., Chance, R., Heath, H.E., Di-Marin, R.D., Di Cera, E., and Williamson, J.R. (1997) Prevention of Vascular and Neuronal Dysfunction in Diabetic Rat by c-Peptide, Science 277, 563–566.

    Article  PubMed  CAS  Google Scholar 

  42. Steiner, D.E., and Rubenstein, A.M. (1997) Proinsulin c-Peptide—Biological Activity?, Science 277, 531–532.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390 002, Gujarat, India

    Samir P. Patel & Surendra S. Katyare

Authors
  1. Samir P. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Surendra S. Katyare
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samir P. Patel.

About this article

Cite this article

Patel, S.P., Katyare, S.S. Insulin-status-dependent modulation of FoF1-ATPase activity in rat liver mitochondria. Lipids 41, 695–703 (2006). https://doi.org/10.1007/s11745-006-5020-y

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-006-5020-y

Keywords

Search

Navigation