Skip to main content
SpringerLink
Log in

Inhibition of cellular autophagy in proximal tubular cells of the kidney in streptozotocin-diabetic and uninephrectomized rats

  • Original Articles
  • Published:
Virchows Archiv B

Summary

To examine the significance of anti-catabolism in renal hypertrophy, cellular autophagy was investigated by electron microscopic morphometry in proximal tubular cells (PTCs) of the outer cortex of the rat kidney after the induction of diabetes mellitus by streptozotocin (STZ) and after unilateral nephrectomy. Adult male Sprague-Dawley rats were divided into three groups and killed by retrograde perfusion fixation, 1, 2 and 3 days after the induction of diabetes (group D; n=24), after unilateral nephrectomy (group N; n=24) and after combined treatment (group DN; n=24). Untreated, agematched litter mates served as controls (group C; n=24). By comparison with these controls, the left kidney to initial body weight ratio was increased by 8, 23, and 15% in group D animals, by 8, 23, and 24% in group N animals, and by 10, 21, and 25% in group DN animals at the first, second and third day, respectively. Quantitative evaluation of large test areas showed that the volume and numerical densities of autophagic vacuoles (AVs) in PTCs were significantly lower in these hypertrophed kidneys than in the controls. The average reduction in AV volume density was about 65% in group D animals, about 50% in group N animals and about 75% in group DN animals. These data show that autophagic degradation of cytoplasmic components in PTCs is inhibited in renal hypertrophy independently of the growth stimulus, i.e. uninephrectomy or diabetes. Since insulin per se inhibits cellular autophagy in PTCs, the expected effect of insulin dificiency seems to be counteracted by as yet undefined stimuli that may be related to metabolic work load.

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

References

  • Bahro M, Gertig G, Pfeifer U (1988) Short-term stimulation of cellular autophagy by furosemide in the thick ascending limb of Henle’s loop in the rat kidney. Cell Tiss Res 253: 625–629

    Article  CAS  Google Scholar 

  • Bank N, Lahorra MAG, Aynedjian HS, Schlondorff D (1988) Vasoregulatory hormones and the hyperfiltration of diabetes. Am J Physiol 254: F202-F209

    PubMed  CAS  Google Scholar 

  • Brosky G, Sogothethopoulos J (1971) Streptozotocin diabetes in the mouse and guinea pig. Diabetes 18: 606–611

    Google Scholar 

  • Chevalier RL (1982) Functional adaptation to reduced renal mass in early development. Am J Physiol 242: F190-F196

    PubMed  CAS  Google Scholar 

  • Dämmrich J, Pfeifer U (1983) Cardiac hypertrophy in rats after supravalvular aortic constriction II. Inhibition of cellular autophagy in hypertrophying cardiomyocytes. Virchows Arch [B] 43: 287–307

    Google Scholar 

  • Fine LG (1986) The biology of renal hypertrophy. Kidney Int 29: 619–634

    Article  PubMed  CAS  Google Scholar 

  • Finn WF (1982) Compensatory renal hypertrophy in Sprague-Dawley rats. Glomerular ultrafiltration dynamics. Renal Physiol [Basel] 5: 222–234

    CAS  Google Scholar 

  • Fleck CH, Bräunlich H (1984) Kidney function function after unilateral nephrectomy. Exp Pathol 25: 3–18

    PubMed  CAS  Google Scholar 

  • Flyvbjerg A, Thorlacius-Ussing O, Naeraa R, Ingerslev J, Orskov H (1988) Kidney tissue somatomedin C and initial renal growth in diabetic and uninephrectomised rats. Diabetologia 31: 310–314

    PubMed  CAS  Google Scholar 

  • Furuno K, Ishikawa T, Kato K (1982) Appearence of autolysosomes in rat liver after leupeptin treatment. J Biochem 91: 1485–1491

    PubMed  CAS  Google Scholar 

  • Gittes GK, Gittes RF (1984) The effect of ureteroperitoneostomy on renal mass in fasted rats. J Urol 131: 1206–1207

    PubMed  CAS  Google Scholar 

  • Glaumann H, Eriksson JLE, Marzella L (1981) Mechanisms of intralysosomal degradation with special reference to auto- phagocytosis and heterophagocytosis of cell organelles. Int Rev Cytol 73: 149–182

    PubMed  CAS  Google Scholar 

  • Glaumann H, Ahlberg J (1987) Comparison of different autophagic vacuoles with regard to ultrastructure, enzymatic composition and degradation capacity formation of crinosomes. Exp Mol Pathol 47: 346–362

    Article  PubMed  CAS  Google Scholar 

  • Harris RC, Brenner BM, Seifer JL (1986) Sodium-hydrogen exchange and glucose transport in renal microvillus membrane vesicles from rats with diabetes mellitus. J Clin Invest 77: 724–733

    Article  PubMed  CAS  Google Scholar 

  • Hayslett JP (1979) Functional adaptation to reduction in renal mass. Physiol Rev 59: 137–164

    PubMed  CAS  Google Scholar 

  • Henell F, Glaumann H (1984) Effect of leupeptin on the autophagic vacuolar system of rat hepatocytes. Correlation between ultrastructure and degradation of membrane and cytosolic proteins. Lab Invest 51: 46–56

    PubMed  CAS  Google Scholar 

  • Henell F, Berkenstam A, Ahlberg J, Glaumann H (1987) Degradation of short- and long-lived proteins in perfused liver and in isolated autophagic vacuoles-lysosomes. Exp Mol Pathol 46: 1–14

    Article  PubMed  CAS  Google Scholar 

  • Hill JM, Malamud D (1974) Decreased protein catabolism during stimulated growth. FEBS Lett 46: 308–311

    Article  PubMed  CAS  Google Scholar 

  • Hirose K, Tsuchida H, Osterby R, Gundersen HJG (1980) A strong correlation between glomerular filtration rate and filtration surface in diabetic kidney hyperfunction. Lab Invest 43: 434–437

    PubMed  CAS  Google Scholar 

  • Hostetter TH, Olson JL, Reunke HG, Venkatachalam MA, Brenner BM (1981) Hyperfiltration in remmant nephrons: a potentially adverse response to ablation. Am J Physiol 241: F85-F93

    PubMed  CAS  Google Scholar 

  • Jensen PK, Christiansen JS, Steven K, Parving HH (1981) Renal function in streptozotocin diabetic rats. Diabetologia 21: 409–414

    Article  PubMed  CAS  Google Scholar 

  • Jurilj N, Pfeifer U (1985) Hemmung der cellulären Autophagie im Nierentubulus als frühe Reaktion nach unilateraler Nephrektomie. Verh Dtsch Ges Pathol 69: 479

    Google Scholar 

  • Jurilj N, Pfeifer U (1990) Inhibition of cellular autophagy in kidney tubular cells stimulated to grow by unilateral nephrectomy. Virchows Arch [B] 59: 32–37

    CAS  Google Scholar 

  • Katz AL, Toback FG, Lindheimer MD (1978) The role of renal “work” in compensatory kidney growth. Yale J Biol Med 51: 331–337

    PubMed  CAS  Google Scholar 

  • Kleinman KS, Fine LG (1988) Prognostic implications of renal hypertrophy in diabetes mellitus. Diabetes [Metab Rev] 4: 179–189

    Article  CAS  Google Scholar 

  • Krostrup JP, Gundersen HJG, Osterby R (1977) Glomerular size and structure in diabetes mellitus III. Early enlargement of the capillary surface. Diabetologia 13: 207–210

    Article  Google Scholar 

  • Ku DD, Roberts RB, Sellers BM, Meezan E (1987) Regression of renal hypertrophy and elevated renal Na+, K+-ATPase activity after insulin treatment in streptozotocin-diabetic rats. Endocrinology 120: 2166–2173

    PubMed  CAS  Google Scholar 

  • Kunjara S, Sochor M, Greenbaum AL, McLean P (1986) Concentration of phosphoribosyl pyrophosphate in renal hypertrophy. Contrasting effects of early diabetes and unilateral nephrectomy. Biochem J 239: 241–244

    PubMed  CAS  Google Scholar 

  • Kunjara S, Beardsley SJ, Greenbaum AL (1988) Renal hypertrophy in experimental diabetes. The activity of the “de novo” and salvage pathways of protein synthesis. Biochem J 249: 911–914

    PubMed  CAS  Google Scholar 

  • Lee CS, Maner SM, Brown DM, Sutherland DER, Michel AF, Najarian JS (1984) Renal transplantation in diabetes mellitus in rats. J Exp Med 139: 793–800

    Article  Google Scholar 

  • Luft JH (1961) Improvements in epoxy resin embedding methods. J Biophys Biochem Cytol 9: 409–414

    Article  PubMed  CAS  Google Scholar 

  • Marzella L, Glaumann H (1980) Increased degradation in rat liver induced by vimblastine II. Morphological characterization. Lab Invest 42: 18–27

    PubMed  CAS  Google Scholar 

  • Millonig G (1962) Further observations on a phosphate buffer for osmium solutions in fixation. Proc Vth Int. Congress electron microscopy, Philadelphia, vol 2. Academic Press, New York London, p 8

    Google Scholar 

  • Mogensen CE, Osterby R, Gundersen HJG (1979) Early functional and morphologic vascular renal consequences of the diabetic state. Diabetologia 17: 71–76

    Article  PubMed  CAS  Google Scholar 

  • Mogensen CE, Steffes MW, Deckert T, Christiansen JS (1981) Functional and morphological renal manifestations in diabetes mellitus. Diabetologia 21: 89–93

    Article  PubMed  CAS  Google Scholar 

  • Müller J, Pfeifer U, Dämmrich J (1987) Inhibited autophagic degradation uring ACTH-stimulated growth of rat adrenal zona fasciculata. Virchows Arch [B] 52: 429–442

    Article  Google Scholar 

  • Osterby R, Seyer-Hansen K, Gundersen HJG (1978) Rapid increase in filtration surface and basement membrane material in acute diabetes. Diabetologia 15: 259

    Article  Google Scholar 

  • Osterby R (1986) Structural changes in the diabetic kidney. Clin Endocrinol Metab 15: 733–751

    PubMed  CAS  Google Scholar 

  • Pain VM, Garlick PJ (1974) Effect of streptozotocin diabetes and insulin treatment on the rate of protein synthesis in tissues of the rat in vivo. J Biol Chem 249: 4510–4514

    PubMed  CAS  Google Scholar 

  • Pfeifer U (1976) Lysosomen und Autophagie. Verh Dtsch Ges Path, 60: 28–64, 1976

    Google Scholar 

  • Pfeifer U (1978) Inhibition by insulin of the formation of autophagic vacuoles in rat liver. A morphometric approach to the kinetics of intracellular degradation by autophagy. J Cell Biol 78: 152–167

    Article  PubMed  CAS  Google Scholar 

  • Pfeifer U (1982) Kinetic and subcellular aspects of hypertrophy and atrophy. Int Review Exp Pathol 23: 1–45

    CAS  Google Scholar 

  • Pfeifer U, Scheller H (1975) A morphometric study of cellular autophagy including diurnal variations in kidney tubules of normal rats. J Cell Biol 64: 608–621

    Article  PubMed  CAS  Google Scholar 

  • Pfeifer U, Bertling J (1977) A morphometric study of the inhibition of autophagic degradation during restorative growth of liver cells in rats re-fed after starvation. Virchows Arch [B] 24: 109–120

    CAS  Google Scholar 

  • Pfeifer U, Jurilj N (1979) Hemmung des intrazellulären Organellenabbaues als Prinzip der Wachstumsregulation in Leber und Niere. Verh Dtsch Ges Pathol, 63: 503

    Google Scholar 

  • Pfeifer U, Warmuth-Metz M (1983) Inhibition by insulin of cellular autophagy in proximal tubular cells of rat kidney. Am J Physiol 244 [Endocrinol Metab 7]: E109-E114

    PubMed  CAS  Google Scholar 

  • Pfeifer U, Föhr J, Wilhem W, Dämmrich J (1987) Short-term inhibition of cardiac cellular autophagy by isoproterenol. J Mol Cell Cardiol 19: 1179–1184

    Article  PubMed  CAS  Google Scholar 

  • Rasch R, Rytter-Nörgaard JO (1983) Renal enlargement: comparative autoradiographic studies of 3H-thymidine uptake in diabetic and uninephrectomised rats. Diabetologia 25: 280–287

    Article  PubMed  CAS  Google Scholar 

  • Richardson KC, Jarett L, Finke EH (1960) Embedding in epoxy resins for ultrathin sectioning in electron microscopy. Stain Technol 35: 313–323

    PubMed  CAS  Google Scholar 

  • Ross J, Goldman JK (1971) Effect of streptozotocin-induced diabetes on kidney weight and compensatory hypertrophy in the rat. Endocrinology 88: 1079–1082

    PubMed  CAS  Google Scholar 

  • Seglen PO, Grinde B, Solheim AL (1979) Inhibition of the lysosomal pathway of protein degradation in isolated rat hepatocytes by hepatocytes by ammonia, methylamine, chloroquine and leupeptin. Eur J Biochem 95: 215–225

    Article  PubMed  CAS  Google Scholar 

  • Seyer-Hansen K (1976) Renal hypertrophy in streptozotocin-diabetic rats. Clin Sci Mol Med 51: 551–555

    CAS  Google Scholar 

  • Seyer-Hansen K (1978) Renal hypertrophy in experimental diabetes: a comparation to compensatory hypertrophy. Diabetologia 14: 325–328

    Article  PubMed  CAS  Google Scholar 

  • Seyer-Hansen K (1983) Renal hypertrophy in experimental diabetes mellitus. Kidney Int 23: 643–646

    Article  PubMed  CAS  Google Scholar 

  • Seyer-Hansen K (1987) Renal hypertrophy in experimental diabetes: some functional aspects. J Diabetic Complic 1: 7–10

    Article  CAS  Google Scholar 

  • Viberti GC, Wiseman MJ (1986) The kidney in diabetes: significance of the early abnormalities. Clin Endocrinol Metab 15: 785–782

    Article  Google Scholar 

  • Wald H, Popovtzer MM (1984) The effect of streptozotocin induced diabetes mellitus on urinary excretion of sodium and renal Na+, K+-ATPase activity. Pfluegers Arch 401: 97–100

    Article  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centro de Pesquisas Conçalo Moniz (FIOCRUZ), R. Valdemar Falcao, 121-Brotas, 40.000, Salvador, Bahia, Brazil

    Aryon de Almeida Barbosa

  2. Department of Pathology, University of Bonn, Postfach 2121, W-5300, Bonn, Federal Republic of Germany

    Hui Zhou, Dieter Hültenschmidt, Vladimir Totovic & Ulrich Pfeifer

  3. Department of Biology, Stomatological Faculty, University of Zagreb, Yugoslavia

    Nenad Jurilj

Authors
  1. Aryon de Almeida Barbosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hui Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dieter Hültenschmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vladimir Totovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nenad Jurilj
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ulrich Pfeifer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barbosa, A.d.A., Zhou, H., Hültenschmidt, D. et al. Inhibition of cellular autophagy in proximal tubular cells of the kidney in streptozotocin-diabetic and uninephrectomized rats. Virchows Archiv B Cell Pathol 61, 359–366 (1992). https://doi.org/10.1007/BF02890439

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02890439

Key words

Search

Navigation