Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Effect of duration of insulin deficiency on membrane-bound and free ribosomes from livers of diabetic rats


In order to define the effect of duration of diabetes on hepatic protein synthesis, membrane-bound and free ribosomes were isolated from livers of rats, 3, 7 and 28 days after administration of intravenous streptozotocin (75 mg/kg). Hepatocytes from the same rats were subjected to ultrastructural quantitative analysis. By day 3 there was a significant loss in the amount of rough endoplasmic reticulum (RER) per volume cytoplasm; however, the normal ratio of membrane-bound ribosomes per unit length of membrane was maintained. These hepatocyte ultrastructural changes continued over the ensuing four weeks. In spite of this decrease in amount of RER, in vitro protein synthetic activity of hepatic membrane-bound polyribosomes was unchanged from controls at three days, and by 28 days protein synthetic activity of bound hepatic ribosomes from diabetic rats was almost twice that of normal controls (p <.01). In contrast to the effect of diabetes on bound ribosomes, there was no change in protein synthetic activity of free polyribosomes isolated from livers of rats, 3, 7 or 28 days after induction of diabetes. Thus, the effect of any given degree of diabetes on hepatic protein synthesis appears to vary with the population of hepatic ribosomes being studied, and with duration of insulin deficiency.


  1. 1.

    Tragl, K. H., Reaven, G. M.: Effect of experimental diabetes mellitus on protein synthesis by liver ribosomes. Diabetes 20, 27–32 (1971)

  2. 2.

    Reaven, E. P., Peterson, D. T., Reaven, G. M.: The effect of experimental diabetes mellitus and insulin replacement on hepatic ultrastructure and protein synthesis. J. clin. Invest. 52, 248–262 (1973)

  3. 3.

    Peterson, D. T., Alford, F. P., Ueyama, I., Reaven, E. P., Reaven, G. M.: Characteristics of membrane bound and free hepatic ribosomes from insulin deficient rats. I. Acute experimental diabetes mellitus. J. clin. Invest. 52, 3201–3211 (1973)

  4. 4.

    Redman, C. M.: Biosynthesis of serum proteins and ferritin by free and attached ribosomes of rat liver. J. biol. Chem. 244, 4308–4315 (1969)

  5. 5.

    Takagi, M., Tanaka, T., Ogata, K.: Functional differences in protein synthesis between free and bound polysomes of rat liver. Biochim. biophys. Acta (Amst.) 217, 148–158 (1970)

  6. 6.

    Junod, A., Lambert, A. E., Stauffacher, W., Renold, A. E.: Diabetogenic action of streptozotocin: Relationship of dose to metabolic response. I. clin. Invest. 48, 2129–2139 (1969)

  7. 7.

    Murphy, E. D., Anderson, J. W.: Tissue glycolytic and gluconeogenic enzyme activities in mildly and moderately diabetic rats: Influence of tolbutamide administration. Endocrinology 94, 27–34 (1974)

  8. 8.

    Blobel, G., Potter, V. R.: Studies on free and membrane bound ribosomes in rat liver. I. Distribution as related to total cellular RNA. J. molec. Biol. 26, 279–292 (1967)

  9. 9.

    Blobel, G., Potter, V. R.: Studies on free and membrane bound ribosomes in rat liver. II. Interaction of ribosomes and membranes. J. molec. Biol. 26, 293–302 (1967)

  10. 10.

    Blobel, G., Potter, V. R.: Relation of ribonuclease and ribonuclease inhibitor to the isolation of polysomes from rat liver. Proc. nat. Acad. Sci. (Wash.) 55, 1283–1288 (1966)

  11. 11.

    Peterson, D. T., Greene, W. C., Reaven, G. M.: The effect of experimental diabetes on kidney ribosomal protein synthesis. Diabetes 20, 649–654 (1971)

  12. 12.

    Richardson, A., McGown, E., Henderson, L. M., Swan, P. B.: In vitro amino acid incorporation by the post mitochondrial supernatant of rat liver. Biochim. biophys. Acta (Amst.) 254, 468–477 (1971)

  13. 13.

    Hogland, M. B., Stephenson, M. L., Scott, J. F., Hecht, L. C., Zamecnik, P. C.: A soluble ribonucleic acid intermediate in protein synthesis. J. biol. Chem. 231, 241–257 (1958)

  14. 14.

    Loud, A. V.: A quantitative stereological description of the ultrastructure of normal rat liver parenchymal cells. J. Cell Biol. 37, 27–46 (1968)

  15. 15.

    Weibel, E. R.: Stereological principles for morphometry in electron microscopic cytology. Int. Rev. Cytol. 26, 235–302 (1969)

  16. 16.

    Mazzaferri, E. L., Stillman, G., Lanese, R. R., Keller, M. P.: Use of test strips with colour meter to measure blood-glucose. Lancet 1970 I, 331–333

  17. 17.

    Fleck, A., Munro, H. N.: The precision of ultraviolet absorption measurements in the Schmidt-Thannhauser procedure for nucleic acid estimation. Biochim. biophys. Acta (Amst.) 55, 571–583 (1962)

  18. 18.

    Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the folin phenol reagent. J. biol. Chem. 193, 265–275 (1951)

  19. 19.

    Kimberg, D. V., Yelding, K. L.: Pyruvate kinase. Structural and functional changes induced by diethylstilbestrol and certain steroid hormones. J. biol. Chem. 237, 3233–3239 (1962)

  20. 20.

    Ballard, F. J., Hanson, R. W.: Phosphoenol pyruvate carboxykinase and pyruvate carboxylase in developing liver. Biochem. J. 104, 866–871 (1967)

  21. 21.

    Segal, H. L., Washko, M. E.: Studies of liver glucose 6-phosphotase. Solubilization and properties of the enzyme from normal and diabetic rats. J. biol. Chem. 234, 1937–1941 (1959)

  22. 22.

    Wool, I. G., Stirewalt, W. S., Kurihara, K., Low, R. B., Bailey, P., Oyer, D.: Hormones and metabolic function. Mode of action of insulin in regulation of protein synthesis in muscle. Recent Progr. Hormone Res. 24, 139–213 (1968)

  23. 23.

    Manchester, K. L.: Effect of insulin on protein synthesis. Diabetes 21 (suppl. 2), 447–452 (1972)

  24. 24.

    Baliga, B. S., Pronczuk, A. W., Munro, H. N.: Regulation of polysome aggregation in a cell-free system through amino acid supply. J. molec. Biol. 34, 199–218 (1968)

  25. 25.

    Nolan, R. D., Hoadland, M. B.: Cytoplasmic control of protein synthesis in rat liver. Biochim. biophys. Acta. (Amst.) 247, 609–620 (1971)

Download references

Author information

Additional information

This work was supported in part by funds from the Veterans Administration, from NHLI Research Grant #HL 08506, and from the Evelyn L. Neizer Fund. These studies were presented in part at the 33rd Annual Meeting of the American Diabetes Association, Chicago, 111. June 23–24, 1973.

Dr. Alford is a Beecham Travelling Fellow of the Royal Australian College of Physicians.

Dr. Reaven is a Medical Investigator (MRIS #7363), Veterans Administration.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Alford, F.P., Millea, M.E., Reaven, E.P. et al. Effect of duration of insulin deficiency on membrane-bound and free ribosomes from livers of diabetic rats. Diabetologia 11, 191–200 (1975).

Download citation

Key words

  • Insulin deficiency
  • protein synthesis
  • hepatic ribosomes
  • diabetic ribosomes