Skip to main content

Normalization of hepatic lysosomal autophagy in streptozotocin diabetic rats after pancreatic transplantation

Virchows Archiv B volume 43, pages 189–197 (1983)Cite this article

Summary

This study was performed to determine whether the enhanced hepatic autophagocytosis occurring in diabetes mellitus could be reversed by pancreatic transplantation despite the persistence of hyperglucagonemia in transplant recipients. Twenty weeks after pancreatic transplantation, hepatic lysosomes and autophagic vacuoles were quantitated morphometrically in untreated streptozotocin-diabetic rats and in streptozotocin-diabetic rats treated by pancreatic transplantation. Hyperglycemia and hypoinsulinemia in untreated diabetic rats were corrected after pancreatic transplantation. However, the peripheral plasma glucagon concentration remained significantly higher in transplant recipients than in non-diabetic controls. Light microscopic morphometry revealed no significant effect of the diabetic state or its reversal on the volume of the single hepatocyte or the volume density and numerical density of hepatocytes. However, electron microscopic examination showed that the number and volume density of lysosomes and autophagic vacuoles, which were significantly increased in diabetic rats, returned to control values after pancreatic transplantation. It is concluded that chronic hyperglucagonemia does not preserve enhanced hepatic autophagocytosis when the diabetic hypoinsulinemia is corrected by the pancreatic transplant.

This is a preview of subscription content, access via your institution.

References

  • Amherdt M, Harris V, Renold AE, Orci L, Unger RH (1974) Hepatic autophagy in uncontrolled experimental diabetes and its relationship to insulin and glucagon. J Clin Invest 54:188–193

    PubMed  Article  CAS  Google Scholar 

  • Aronson NN, Jr (1980) Effects of glucagon and insulin on liver lysosomes (minireview) Life Sci 27:95–104

    PubMed  Article  CAS  Google Scholar 

  • Ashford TP, Porter KR (1962) Cytoplasmic components in hepatic cell lysosomes. J Cell Biol 12:198–202

    PubMed  Article  CAS  Google Scholar 

  • Bhathena SJ, Voyles NR, Smith S, Recaut L (1978) Decreased glucagon receptors in diabetic rat hepatocytes: Evidence for regulation of glucagon receptors by hyperglucagonemia. J Clin Invest 61:1488–1497

    PubMed  Article  CAS  Google Scholar 

  • Brekke IB, Gullesen J, Refsum SB, Flatmark A (1980) Long-term endocrine function of ductligated pancreas isotransplants in rats. Eur Surg Res 12:167–178

    PubMed  Article  CAS  Google Scholar 

  • Brekke IB, Høstmark AT, Flaten O (1981) Effect of pancreas transplantation on plasma lipids and plasma concentrations of pancreatic hormones in streptozotocin-diabetic rats. Eur Surg Res 13:361–370

    PubMed  Article  CAS  Google Scholar 

  • Brekke IB, Øyasæter S, Vidnes J (1982a) Long term effect of pancreas transplantation on diabetic hyperglucagonemia. Eur Surg Res 14:211–220

    PubMed  Article  CAS  Google Scholar 

  • Brekke IB, Schmidt E, Schmidt FW (1982b) Effect of pancreas transplantation on liver carbohydrate metabolism in streptozotocin diabetic rats. J Clin Chem Clin Biochem 20:81–84

    PubMed  CAS  Google Scholar 

  • Cherrington A, Vranic M (1974) Effect of interaction of insulin and glucagon on glucose turnover and FFA concentration in normal and depancreatized dogs. Metab Clin Exp 27:729–744

    Google Scholar 

  • Daems WT, Wisse E, Brederoo P (1969) Electron microscopy of the vacuolar apparatus. In: Dingle JT, Fell HB (eds) Lysosomes in biology and pathology. North Holland Publishing Co., Amsterdam, p 64

    Google Scholar 

  • De Duve C, Wattiaux R (1966) Function of lysosomes. Ann Rev Physiol 28:435–492

    Article  Google Scholar 

  • Desai ID (1969) Regulation of lysosomal enzymes. I. Adaptive changes in enzyme activities during starvation and refeeding. Can J Biochem 47:785–790

    PubMed  Article  CAS  Google Scholar 

  • Deter RL, De Duve C (1967) Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes. J Cell Biol 33:437–449

    PubMed  Article  CAS  Google Scholar 

  • Gundersen HJG (1977) Notes on the estimation of the numerical density of arbitrary profiles: the edge effect. J Microsc 111:219–223

    Google Scholar 

  • Hales CN, Randle PJ (1963) Immunoassay of insulin with insulin-antibody precipitate. Biochem J 88:137–146

    PubMed  CAS  Google Scholar 

  • Heding LG (1971) Radioimmunological determination of pancreatic and gut glucagon in plasma. Diabetologia 7:10–19

    PubMed  Article  CAS  Google Scholar 

  • Hershko A, Ciechanover A (1982) Mechanisms of intracellular protein breakdown. Ann Rev Biochem 51:335–364

    PubMed  Article  CAS  Google Scholar 

  • Huggett ASG, Nixon DA (1957) Use of glucose oxidase, perioxidase and O-dianisidine in determination of blood and urinary glucose. Lancet II: 368–370

    Article  Google Scholar 

  • Khairallah EA, Airhart J, Bruno MK, Puchalsky D, Khairallah L (1977) Implications of amino acid compartmentation for the determination of rates of protein catabolism in livers in meal fed rats. Acta Biol Med Germ 36:1735–1745

    PubMed  CAS  Google Scholar 

  • Marzella L, Ahlberg J, Glaumann H (1981) Autophagy, heterophagy, microautophagy and crinophagy as the means for intra-cellular degradation. Virchows Arch [Cell Pathol] 36:219–234

    Article  CAS  Google Scholar 

  • Mortimore GE, Schworer CM (1980) Application of liver perfusion as an in vitro model in studies of intracellular protein degradation. In: Ciba Foundation symposium. Protein degradation in health and disease. Excerpta Medica, Amsterdam Oxford New York, p 281

    Chapter  Google Scholar 

  • Mortimore GE, Ward WF (1981) Internalization of cytoplasmic protein by hepatic lysosomes in basal and deprivation-induced proteolytic states. J Biol Chem 256:7659–7665

    PubMed  CAS  Google Scholar 

  • Mortimore GE, Ward WF, Schworer CM (1978) Lysosomal processing of intracellular protein in rat liver and its general regulation by amino acids and insulin. In: Segal HL, Doyle DJ (eds) Protein turnover and lysosome function. Academic Press, New York San Francisco London, p 67

    Google Scholar 

  • Pfeifer U (1976) Lysosomen and Autophagie. Verh Dtsch Ges Pathol 60:28–64

    Google Scholar 

  • Pfeifer U (1978) Inhibition by insulin of the formation of autophagic vacuoles in rat liver. J Cell Biol 78:152–167

    PubMed  Article  CAS  Google Scholar 

  • Reith A, Barnard T, Rohr H (1976) Stereology of cellular reaction patterns. CRC Crit Rev Toxicol 4:219–269

    PubMed  CAS  Google Scholar 

  • Rohr HP, Anderes C, Bianchi L (1970) Ultrastrukturell-morphometrische Untersuchungen an der Leberparenchymzelle der Ratte nach Glucagon-Gabe (unter besonderer Berücksichtigung lysosomaler Funktionsformen). Beitr Pathol 141:313–326

    PubMed  CAS  Google Scholar 

  • Rossi GL (1975) Simple apparatus for perfusion fixation for electron microscopy. Experientia 31:998–1000

    PubMed  Article  CAS  Google Scholar 

  • Weibel ER, Stäubli W, Gnägi HR, Hess FA (1969) Correlated morphometric and biochemical studies on the liver cell. I. Morphometric model, stereologic methods, and normal morphometric data for rat liver. J Cell Biol 42:68–91

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. Surgical Department B, Rikshospitalet, The National Hospital, and Laboratory for Electronmicroscopy and Morphometry, Department of Pathology, Norsk Hydro’s Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway

    I. B. Brekke, H. Danielsen & A. Reith

Authors
  1. I. B. Brekke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Danielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Reith
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by grants from Norges Landsforbund for Sukkersyke and Nordic Insulin Fund

Presented as a preliminary report at “Lessons from animal diabetes”. Jerusalem, Nov. 1982

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Brekke, I.B., Danielsen, H. & Reith, A. Normalization of hepatic lysosomal autophagy in streptozotocin diabetic rats after pancreatic transplantation. Virchows Archiv B Cell Pathol 43, 189–197 (1983). https://doi.org/10.1007/BF02932956

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02932956

Key words

  • Glucagon
  • Insulin
  • Morphometry
  • Gluconeogenesis
  • Lysosomes