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The impact of type I diabetes on rat liver γ-glutamyltranspeptidase

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Abstract

The impact of type 1 diabetes mellitus on liver γ-glutamyltranspeptidase, a premalignant marker, was studied. Diabetes was induced in male Sprague Dawley and Fischer 344 rats by administration of Streptozotocin, which produced a stable and moderately severe diabetic state. In liver homogenates, γ-glutamyltranspeptidase was increased over control levels: 1.2, 8.1 and 13,2 fold in Strague-Dawley rats; 4.8, 58.4 and 84.7 fold in Fischer 344 rats; at 1, 3 and 6 weeks following Streptozotocin treatment. In plasma membranes isolated from the livers of Fischer 344 rats, γ-glutamyltranspeptidase was increased over control levels: 5.6, 75 and 127 fold at weeks 1, 3 and 6 following Streptozotocin treatment. The relative specific activity of 5′-nuleohdase was found to be similar: 9–14, indicating comparable degrees of plasma membrane purity. Plasma glutamate-pyruvate transaminase levels were minimally and similarly affected at all time points indicating lack of association of increasing γ-glutamyltranspeptidase activity with overt liver damage. Thyroid hormone replacement, with both T3 (0.6 μg/Kg) once a day and T4 (6.0 μg/kg) twice a day for three days elicited a further 30% increment in enzyme activity. Insulin replacement (20–40 units/200 g body weight) twice a day for five days reduced enzyme activity 51% at week 6. This was associated with an increase in γ-glutamyltranspeptidase in the plasma from 14 fold over control levels in the diabetic state at week 6 to 53 fold ever control levels after insulin replacement at week 6. It is proposed that the diabetes-induced increase in γ-glutamyltranspeptidase is reduced by an insulin-directed shedding of the enzyme into the plasma.

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References

  1. Sulakhe SJ, Lautt WW: The activity of γ-glutamyltranspeptidase in various animal species. Comp Biochem Physiol 82B; 263–264, 1985

    Google Scholar 

  2. Sulakhe SJ, Gilmour THJ, Pulga VB: γ-glutamyltranspeptidase in echinoderm eggs and larvae: fertilization-dependent and developmentallyinduced changes in specific activity. Comp Biochem Physiol 97B: 767–773, 1990

    Google Scholar 

  3. Tate SS, Meister A: γ-glutamyltranspeptidase: catalytic, structural and functional aspects. Molec Cell Biochem 39: 357–368, 1981

    PubMed  Google Scholar 

  4. Sulakhe SJ, Lautt WW: A characterization of γ-glutamyltranspeptidase in normal, perinatal, premalignant and malignant rat liver. Int J Biochem 19: 23–32, 1987

    PubMed  Google Scholar 

  5. Fiala S, Fiala ES: Activation by chemical carcinogens of γ-glutamyltranspeptidase in rat and mouse liver. J Natl Cancer Instit 51: 151–158, 1973

    Google Scholar 

  6. Farber, E: Experimental induction of hepatocellular carcinoma as a paradigm for carcinogenesis. Clin Physiol and Biochem 5: 152–159, 1987

    Google Scholar 

  7. Sulakhe-Hemmings, SJ, Pulaa VB, Tran ST: An extended developmental study of γ-glutamyltranspeptidase: identification of specific patterns of changes in activity in the adult as well as the neonatal state. Molec Cell Biochem 115: 71–77, 1992

    PubMed  Google Scholar 

  8. Hanigan, MH, Pitot HC: γ-glutamyltranspeptidase: its role in hepatocarcinogenesis. Carcinogenesis 6: 168–172, 1985

    Google Scholar 

  9. Sulakhe SJ, Tran ST, Pulga VB: Modulation of γ-glutamyltranspeptidase activity in rat liver plasma membranes by thyroid hormone. Int J Biochem 22: 997–1004, 1990

    PubMed  Google Scholar 

  10. Sulakhe, SJ, Pulga VB, Tran ST: Diethylnitrosamine-induced increase in γ-glutamyltranspeptidase in rat live: its association with thyroid hormone deficiency and its reversal by triiodothyronine. Int J Biochem 24: 643–651, 1992

    PubMed  Google Scholar 

  11. Pittman CS, Suda AK, Chambers JB: Impaired 3,5,3′-triiodothyronine (T3) production in diabetic patients. Metabolism 28: 333–338, 1979

    PubMed  Google Scholar 

  12. Sigemasa C, Abe K, Taniguchi S, Mitani Y, Ueta Y, Adachi T, Urabe K, Tanaka T, Yoshida A, Hori T, Mashiba H: The influence of diabetes mellitus of thyrotropin-releasing hormone in untreated acromegalic patients. J Endocrinol Invest 11: 231–237, 1988

    PubMed  Google Scholar 

  13. Tahiliani AG, McNiell JH: Prevention of diabeter-induced myocardial dysfunction in rats by methyl palmoxirate and triiodothyronine treatment. Can J Physiol Pharmacol 63: 925–931, 1981

    Google Scholar 

  14. Dillman WH: Influence of thyroid hormone administration on myosin ATPase activity and myosin isoenzyme distribution in the heart of diabetic rats. Metabolism 31: 199–203, 1982

    PubMed  Google Scholar 

  15. Tahiliani AG, McNeill JH: Lack of effect of thyroid hormone on diabetic rat heart function and biochemistry. Can J Physiol Pharmacol 62: 617–621, 1983

    Google Scholar 

  16. Sundaresan PR, Sharma VK, Gingold SI, Banerjee SP: Decreased β-adrenergic receptors in rat heart in Streptozotocin-induced diabetes: role of thyroid hormone. Endocrinology 114: 1358–1363, 1984

    PubMed  Google Scholar 

  17. Barbee RW, Shepherd RE, Burns AH: T3 treatment does not prevent myocardial dysfunction in chronically diabetic rats. Am J Physiol 254: H265-H273, 1988

    PubMed  Google Scholar 

  18. Grassby PF, NcNeill JH: Sensitivity changes to inotropic agents in rabbit atria after chronic experimental diabetes. Can J Physiol Pharmacol 66: 1475–1480, 1988

    PubMed  Google Scholar 

  19. Legaye F, Beigelman P, Deroubaix E, Coraboeuf E: Effect of 3-5-3-triiodothyronine treatment on cardiac action potential of Streptozotocin-induced diabetic rat. Life Sciences 42: 2269–2274, 1988

    PubMed  Google Scholar 

  20. Volk W, Wellman KF: Cancer and Diabetes. In: W Vclk, KF Wellman (eds) The Diabetic Pancreas. Plenum Press, New York, 1977, p. 311–316

    Google Scholar 

  21. Adami HO, McLaughlin J, Ekbom A, Berne C, Silverman D, Hacker D, Persson I: Cancer risk in patients with diabetes mellitus. Cancer causes Control 2: 307–314, 1991

    PubMed  Google Scholar 

  22. Liver Cell Cancer. HM Cameron, CA Linsell, GP Warwick (eds). Elsevier Scientific Publishing Company, New York, 1976, p. 37

    Google Scholar 

  23. Flatt PR, Bass SL, Ayrton AD, Trinick J, Ionnides C: Metabolic activation of chemical carcinogens by hepatic preparations from Streptozotocin treated rats. Diabetologia 32: 135–139, 1989

    PubMed  Google Scholar 

  24. Yamazoe Y, Abu-Zied M, Yamauchi K, Murayama N, Shimada M, Kato R: Enhancement by alloxan-induced diabetes of the rate of metabolic activation of three pyrolysate carcinogens via increase in the P-448H content in rat liver. Biochem Pharmacol 37: 2503–2506, 1988

    PubMed  Google Scholar 

  25. Porter TD, Coon MJ: Cytochrome P-450. Multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms. J Biol Chem 266: 13469–13472, 1991

    PubMed  Google Scholar 

  26. Funae Y, Imaoke S, Shimojo N: Purification and characterization of diabetes-inducible cytochrome P450. Biochemistry International 16, 503–509, 1988

    PubMed  Google Scholar 

  27. Favreau LV, Schenkman JB: Composition changes in hepatic microsomal cytochrome P-450 during onset of Streptozotocin-induced diabetes and during insulin treatment. Diabetes 37: 577–584, 1991

    Google Scholar 

  28. Degawa M, Tanimura S, Agatsuma T, Hashimoto Y: Hepato-carcinogenic heterocyclic aromatic aminers that induce cytochrome P-448 isozymes, mainly cytochrome P-448H (P-450A2), responsible for mutagenic activation of the carcinogens in rat liver. Carcinogenesis 10: 1119–1122, 1989

    PubMed  Google Scholar 

  29. Bell, RH, Hye RJ: Animal models of diabetes mellitus: physiology and pathology. J Surg Res 35: 443–460, 1983

    Google Scholar 

  30. Sulakhe SJ: The activity of γ-glutamyltraspeptidase in regenerating rat liver. FEBS Letters 204: 302–306, 1986

    PubMed  Google Scholar 

  31. Sulakhe SJ: γ-glutamyltranspeptidase in dimethylbenz [a] anthracene-induced mammary adenocarcinomas and in livers of tumor bearing rats. Int J Biochem 19: 509–515, 1987

    PubMed  Google Scholar 

  32. Sulakhe SJ, Wilson TR: The impact of hypothyroidism and thyroxine replacement on the expression of hepatic α1-, α2- and β-adrenergic receptors. Gen Pharmacol 19: 489–494, 1988

    PubMed  Google Scholar 

  33. Sulakhe SJ, Pulga VB, Tran ST: Calcium transport activities of plasma membranes isolated from the livers of various animal species. Comp Biochem Physiol 96A: 465–468, 1990

    Google Scholar 

  34. Raabo E, Terkildsen TC: On the enzymatic determination of blood glucose. Scand J Clin Invest 12: 402, 1960

    PubMed  Google Scholar 

  35. Williamson DH, Mellanby J, Krebs HA: Enzymatic determination of D(-)β-hydroxybutyric acid and acetoacetic acid in blood. Biochem J 82: 90, 1962

    PubMed  Google Scholar 

  36. Reitman S, Frankel S: A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28: 53–65, 1957

    Google Scholar 

  37. Lowry OH, Rosebrough NJ, Farr AL, Randall RH: Protein measurements with the Folin phenol reagent. J Biol Chem 193: 265–275, 1951

    PubMed  Google Scholar 

  38. Michell RH, Hawthorne JN: The site of diphosphoinositide synthesis in rat liver. Biochem Biophys Res Commun 21: 333–338, 1965

    PubMed  Google Scholar 

  39. Lamas L, Jolin T: Intrathyroidal thyroglobulin in Streptozotocin-diabetic rats. Acta Endocrinologica 112: 552–558, 1986

    PubMed  Google Scholar 

  40. Ikeda T, Ito Y, Murakami I, Mokuda O, Kuno S, Tokumori Y, Tominaga M, Mashiba H: Effect of diabetes on triiodothyronine and reyerse triiodothyronine production in the perfused rat liver and kidney. Diabetes 34: 647–652, 1985

    PubMed  Google Scholar 

  41. Colombo JP, Peheim E, Bachman C, Muller E, Bircher J: γ-glutamyltranspeptidase in the rat liver after portocaval shunt. Ped Res 10: 18–24, 1976

    Google Scholar 

  42. McLennan SV, Heffernan S, Wright L, Rae C, Fisher E, Yue DK, Turtle JR: Changes in hepatic glutathione metabolism in diabetes. Diabetes 40: 344–348, 1991

    PubMed  Google Scholar 

  43. Dillman WJ, Oppenheimer JH: Glucagon influences the expression of thyroid hormone action: discrepancy between nuclear triiodothyronine receptor number and enzyme responses. Endocrinology 105: 74–79, 1979

    PubMed  Google Scholar 

  44. Donati R, Sabolovic N, Wellman M, Artur Y, Siest G: Monoclonal antibodies to human kidney gamma-glutamyltransferase. Clin Chim Acta 174: 149–162, 1988

    PubMed  Google Scholar 

  45. Meeks RG, Harrison SD, Bull RJ: Hepatotoxicology. CRC Press, Boston, 1991

    Google Scholar 

  46. Isawe M, Nunoi K, Sadoshima S, Kikuchi M, Fujishima M: Liver, kidney and islet cell tumors in spontaneously hypertensive and normotensive rats treated neonatally with Streptozotocin. Tohoku J Exp Med 159: 83–90, 1989

    PubMed  Google Scholar 

  47. Thomas H, Schladt L, Knehr M, Oesch F: Effect of diabetes and starvation on the activity of rat liver epoxide hydrolases, glutathione stransferases and peroxisomal β-oxidation. Biochemical Pharmacol 38: 4291–4297, 1989

    Google Scholar 

  48. Robbiano L, Martelli A, Allavena A, Mazzei M, Gazzaniga GM, Brambilla G: Formation of the N-nitroso derivatives of sic p-adrenergic-blocking agents and their genotoxic effects in rat and human hepatocytes. Cancer Res 51: 2273–2279, 1991

    PubMed  Google Scholar 

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  1. Department of Physiology, College of Medicine, University of Saskatchewan, S7N 0W0, Saskatoon, Saskatchewan, Canada

    Susan J. Hemmings & Robert D. Pekush

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  1. Susan J. Hemmings
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Hemmings, S.J., Pekush, R.D. The impact of type I diabetes on rat liver γ-glutamyltranspeptidase. Mol Cell Biochem 139, 131–140 (1994). https://doi.org/10.1007/BF01081736

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  • DOI: https://doi.org/10.1007/BF01081736

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