Skip to main content
NCBI home page
Indian Journal of Clinical Biochemistry logoLink to Indian Journal of Clinical Biochemistry
. 2004 Jul;19(2):23–31. doi: 10.1007/BF02894253

Effect of streptozotocin-induced diabetes on oxidative energy metabolism in rat liver mitochondria—A comparative study of early and late effects

Jagannath G Satav 1,✉, Surendra S Katyare 2,✉
PMCID: PMC3454208  PMID: 23105452

Abstract

The reports in the literature on effects of diabetes on mitochondrial energy-linked functions are conflicting. Hence we carried out systematic studies to evaluate the effects at the early and the late stages of the disease using STZ-diabetic rat as a model. At the end of one week, after induction of diabetes, respiration rates with glutamate and succinate as the substrates increased; respiration rates with other substrates e.g. β-hydroxybutyrate, pyruvate + malate and ascorbate + TMPD were not affected despite substantial decrease in the β-hydroxybutyrate dehydrogenase activity and cytochrome b and c+c1 contents. Insulin treatment brought about increase in the cytochrome contents beyond control values. The ATPase activity was generally low in the diabetic animals and was not restored by insulin treatment.

At the end of one month, the respiratory activities with all the substrates were generally low. Insulin treatment either restored or stimulated the respiration rates beyond control values. The content of cytochromes was differentially affected in the diabetic animals, but insulin treatment caused significant increase beyond control levels. The pattern for ATPase activity was similar to the early effects.

At both the stages i.e. early and late stages of diabetes the mitochondria were tightly coupled. The ADP/O ratios were in normal expected ranges and the respiratory control ratios were comparable with the control groups. Insulin treatment resulted in apparent restoration of respiratory activity. However, the effects on the cytochromes and dehydrogenases activities were differential. Taken together the two observations would suggest that the mitochondria were not re-instated to normality despite apparent restoration of respiratory function.

Key Words: STZ-diabetes, liver mitochondria, energy metabolism, cytochrome profile, ATPase

Full Text

The Full Text of this article is available as a PDF (633.5 KB).

References

  • 1.Alberti K.G.M.M., Press C.M. The biochemistry of the complications of diabetes mellitus. In: Keen M., Jarrett J., editors. Complications of diabetes. London: Edward Arnold Ltd.; 1982. pp. 231–270. [Google Scholar]
  • 2.Cohen M.P. Nonenzymatic glycation and enhanced polyol pathway activity in pathogenesis of diabetic nephropathy. In: Reidland A., Koch K.M., Heidbreder E., editors. Diabetes and the kidney. Basel: Karger; 1989. pp. 59–72. [PubMed] [Google Scholar]
  • 3.Striker G.E., Peten E.P., Carome M.A., Pesce C.M., Schmidt K., Yang C.W., Elliot S.J., Striker L.J. The kidney disease of diabetes mellitus (KDDM). A cell and molecular biology approach. Diabetes/Metabolism Rev. 1993;9:37–56. doi: 10.1002/dmr.5610090105. [DOI] [PubMed] [Google Scholar]
  • 4.Vester J.W., Stadie W.C. Studies of oxidative phosphorylation by hepatic mitochondria from diabetic cats. J. Biol. Chem. 1957;227:669–676. [PubMed] [Google Scholar]
  • 5.Hall J.C., Sordahl L.A., Stefko P.L. The effect of insulin on oxidative phosphorylation in normal and diabetic mitochondria. J. Biol. Chem. 1960;235:1536–1539. [PubMed] [Google Scholar]
  • 6.Matsubara T., Tochino Y. Depression of respiratory activities in the liver mitochondria of rats and restorative action of insulin. J. Biochem. (Japan) 1969;66:397–404. doi: 10.1093/oxfordjournals.jbchem.a129158. [DOI] [PubMed] [Google Scholar]
  • 7.Beyer R.E., Shamoian C.A. Oxidative phosphorylation and related reactions in liver mitochondria from diabetic dogs. Am. J. Physiol. 1961;200:838–840. [Google Scholar]
  • 8.Mackerer C.R., Paquet R.J., Mehlman M.A., Tobin R.B. Oxidation and phosphorylation in liver mitochondria from alloxan and streptozotocin diabetic rats. Proc. Soc. Exptl. Biol. Med. 1971;137:992–995. doi: 10.3181/00379727-137-35712. [DOI] [PubMed] [Google Scholar]
  • 9.Brignone J.A., Campos de Brignone C.M., Rodriguez R.R., Badano B.N., Stoppani A.O.M. Modified oscillation behavior and decreased D-3-hyroxybutyrate dehydrogenase activity in diabetic rat liver mitochondria. Arch. Biochem. Biophys. 1982;214:581–588. doi: 10.1016/0003-9861(82)90063-7. [DOI] [PubMed] [Google Scholar]
  • 10.Bedetti C.D., Montero G.A., Stoppani A.O.M. Effect of diabetes, adrenelalectomy and hypophysectomy on D-3-hyroxybutyrate dehydrogenase activity and substrate oxidation by rat mitochondria. Biochem. Int. 1987;14:45–54. [PubMed] [Google Scholar]
  • 11.Parks R.E., Adler J., Copenhaver J.H. The efficacy of oxidative phosphorylation in mitochondria from diabetic rats. J. Biol. Chem. 1955;214:693–698. [PubMed] [Google Scholar]
  • 12.Marco J.P., Hoppel C. Hepatic mitochondrial function in ketogenic status. Diabetes, starvation and after growth hormone administration. J. Clin. Invest. 1975;55:1237–1244. doi: 10.1172/JCI108042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Rogers K.S., Friend W.H., Higgins E.S. Metabolic and mitochondrial disturbances in streptozotocin-treated Sprague-Dawley and Sherman rats. Proc. Soc. Exptl. Biol. Med. 1986;182:167–175. doi: 10.3181/00379727-182-42323. [DOI] [PubMed] [Google Scholar]
  • 14.Rogers K.S., Higgins E.S., Loria M.R. Influence of genetic predisposition to diabetes and obesity on mitochondrial function. Biochem. Med. Metab. Biol. 1986;35:72–76. doi: 10.1016/0885-4505(86)90060-5. [DOI] [PubMed] [Google Scholar]
  • 15.Katyare S.S., Howland J.L. Enhanced oxidative metabolism in liver mitochondria from genetically obese mice. Arch. Biochem. Biophys. 1978;188:15–20. doi: 10.1016/0003-9861(78)90349-1. [DOI] [PubMed] [Google Scholar]
  • 16.Brady L.J., Brady P.S., Romsos D.R., Hoppel C.L. Elevated hepatic mitochondrial and peroxisomal oxidative capacities in fed and starved adult obese (ob/ob) mice. Biochem. J. 1985;231:439–444. doi: 10.1042/bj2310439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Park C., Drake R.L. Insulin mediates the stimulation of pyruvate kinase by a dual mechanism. Biochem. J. 1982;208:333–337. doi: 10.1042/bj2080333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Berdanier C.D. Diabetes and Nutrition. The mitochondrial part. J. Nutr. 2001;131:344S–353S. doi: 10.1093/jn/131.2.344S. [DOI] [PubMed] [Google Scholar]
  • 19.Gerbitz K-D., Gempel K., Brdiczka D. Mitochondria and Diabetes: Genetic, biochemical, and clinical implications of the cellular energy circuit. Diabetes. 1996;45:113–126. doi: 10.2337/diabetes.45.2.113. [DOI] [PubMed] [Google Scholar]
  • 20.Bessman S.P., Mohan C. Insulin as a probe of mitochondrial metabolism in situ. Mol. Cell. Biochem. 1997;174:91–96. doi: 10.1023/A:1006834408181. [DOI] [PubMed] [Google Scholar]
  • 21.Katyare S.S. Effect of carbonyl cyanide m-chlorophenylhydrazone on oxidative phosphorylation in rat liver mitochondria: Site-specificity of its action. Ind. J. Biochem. Biophys. 1986;23:70–75. [PubMed] [Google Scholar]
  • 22.Katyare S.S., Satav J.G. Impaired mitochondrial oxidative energy metabolism following paracetamol-induced hepatotoxicity in the rat. Br. J. Pharmacol. 1989;96:51–58. doi: 10.1111/j.1476-5381.1989.tb11783.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Nerurkar M.A., Satav J.G., Katyare S.S. Insulin-dependant changes in lysosomal cathepsin D activity in rat liver, kidney, brain and heart. Diabetologia. 1988;31:119–122. doi: 10.1007/BF00395559. [DOI] [PubMed] [Google Scholar]
  • 24.Kumthekar M.M., Katyare S.S. Altered kinetic attributes of Na+ K+ ATPase activity in kidney, brain and erythrocyte membranes in alloxan-diabetic rats. Ind. J. Exptl. Biol. 1992;30:26–32. [PubMed] [Google Scholar]
  • 25.Lowry O.H., Rosebrough N.J., Farr A.L., Randall R.J. Protein measurement with Folin phenol reagent. J. Biol. Chem. 1951;193:265–275. [PubMed] [Google Scholar]
  • 26.Johnson D., Lardy H. In: Isolation of liver or kidney mitochondria. Estabrook R.W., Pullman M.E., editors. New York: Academic; 1967. pp. 94–96. [Google Scholar]
  • 27.Boquist L., Nelson L., Lorentson R. Uptake of labeled alloxan in mouse organs and mitochondria in vivo and in vitro. Endocrinol. 1983;113:943–948. doi: 10.1210/endo-113-3-943. [DOI] [PubMed] [Google Scholar]

Articles from Indian Journal of Clinical Biochemistry are provided here courtesy of Springer

RESOURCES