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Regulation of metabolic pathways in liver and kidney during experimental diabetes: Effects of antidiabetic compounds

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Abstract

Diabetes has been classified as a disease of glucose overproduction by tissues, mainly liver and glucose underutilization by insulin requiring tissues like liver, adipose and muscle due to lack of insulin. There is, however, glucose over utilization in tissues not dependent on insulin for glucose transport like kidney, nerve and brain. There are serious complications due to this excess glucose in these tissues and their reversal is important for a good metabolic control and normalisation of other parameters. Insulin, trace metals and some plant extracts have been used to see the reversal effects of the complications of diabetes in liver and kidney in experimental diabetes. Almost complete reversal of the metabolic changes has been achieved in the activities of key enzymes of metabolic pathways in liver and kidney and an effective glucose control has been achieved suggesting a combination of therapies in the treatment of metabolic disturbance of the diabetic state.

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References

  1. Spiro, R.G. (1976) Search for a biochemical basis of diabetic microangiopathy. Diabetologia 12, 1–4.

    Article  PubMed  CAS  Google Scholar 

  2. McLean, P. (1988) Pancreatic and gastrointestinal hormones. Essentials of Endocrinology Eds. J.L.M. Riordan, P.G. Malan, R.P. Gould, Blackwell Scientific Publication Oxford, England 222–265.

    Google Scholar 

  3. Gabbay, K.H. (1973) The sorbitol pathway and the complication of diabetes. New Engl. J. Med. 288, 831–837.

    Article  PubMed  CAS  Google Scholar 

  4. Bunn, H.F., Shapiro, R., McManns, M., Garrick, L., MacDonald, H.H., Gallop, P.M. and Gabby K.H. (1979) Structural heterogeneity of human haemoglobin A due to non-enzymic glycosylation. J. Biol. Chem. 254, 3892–3898.

    PubMed  CAS  Google Scholar 

  5. Cerami, A., Stevens, V.J. and Monnier, V.M. (1979) Role of nonenzymic glycosylation in the development of the sequence of diabetes mellitus. Metabolism 28 (Suppl 1), 431–437.

    Article  PubMed  CAS  Google Scholar 

  6. Alberti, K.G.M.M. and Press, C.M. (1982) The biochemistry and the complications of diabetes Eds. H. Keen and J. Jarret Edward Arnold Publishers p.231–270.

  7. Sochor, M., Baquer, N.Z. and McLean, P. (1979) Regulation of pathways of glucose metabolism in kidney. The effect of experimental diabetes on the activity of the pentose phosphate pathway and glucuronate-xylulose pathway. Arch. Biochem. Biophys. 198, 632–646.

    Article  PubMed  CAS  Google Scholar 

  8. Sochor, M., Baquer, N.Z., Hothersall, J. and McLean, P. (1990) Effect of experimental diabetes on the activities of hexokinase isoenzymes in tissues of the rat. Biochem. Int., 22 (3), 467–474.

    PubMed  CAS  Google Scholar 

  9. Steer, K.A., Sochor, M., Gonzalez, A.M. and McLean, P. (1982) Regulation of pathway of glucose metabolism in kidney. Specific linking of pentose phosphate pathway activity with kidney growth in experimental diabetes and unilateral nephrectomy. FEBS Lett. 150, 494–498.

    Article  PubMed  CAS  Google Scholar 

  10. Cortes, P., Levin, N.W., Dumler, F., Rubenstein, A.H., Verghese, G.P. and Venkatachalam, K.K. (1980) Uridine triphosphate and RNA-synthesis during diabetes induced kidney growth. Am. J. Physiol. 238E, 349–357.

    Google Scholar 

  11. Oberley, L.W. (1988) Free radicals and diabetes. Free Rad. Biol. Med. 5, 113–124.

    Article  PubMed  CAS  Google Scholar 

  12. Srivastava, P., Saxena, A.K., Kale, R.K. and Baquer, N.Z. (1993) Insulin like effects of lithium and vanadate on the altered antioxidant status of diabetic rats. Res. Commun. Chem. Pathol. Pharmacol. 80(3), 283–293.

    PubMed  CAS  Google Scholar 

  13. Sochor, M., Baquer, N.Z. and McLean, P. (1985) Glucose over and underutilization in diabetes: Comparative studies on the changes in activities of enzymes of glucose metabolism in rat kidney and liver. Mol. Physiol. 7, 51–68.

    CAS  Google Scholar 

  14. Glock, G.E. and McLean, P. (1955) A preliminary investigation of the hormonal control of the hexose monophosphate oxidative pathway. Biochem. J. 61, 397–404.

    PubMed  CAS  Google Scholar 

  15. Novello, F. and McLean, P. (1968) The pentose phosphate pathway of glucose metabolism. Measurement of the non-oxidative reaction of the cycle. Biochem. J. 107, 775–791.

    PubMed  CAS  Google Scholar 

  16. Weinhouse, S. (1976) Regulation of glucokinase in liver. Curr. Topic. Cell. Regul. 11, 1–46.

    CAS  Google Scholar 

  17. Greenbaum, A.L., Gumaa, K.A. and McLean, P. (1971) The distribution of hepatic metabolites and the control of pathways of carbohydrate metabolism in animals of different dietary and hormonal status. Arch. Biochem. Biophys. 143, 617–663.

    Article  PubMed  CAS  Google Scholar 

  18. Needleman, P., Passonnean, J.V. and Lowry, O.H. (1968) Distribution of glucose and related metabolities in rat kidney. Am. J. Physiol. 215, 655–659.

    PubMed  CAS  Google Scholar 

  19. Saxena, A.K., Srivastava, P., Kale, R.K. and Baquer, N.Z. (1992) Effect of vanadate administration on polyol pathway in diabetic rat kidney. Biochem. Int. 26(1), 59–68.

    PubMed  CAS  Google Scholar 

  20. Singh, N., Tyagi, S.D. and Agarwal, S.C. (1989) Effects of long term feeding of acetone extracts ofMomordica charantia (whole fruit powder) on alloxan diabetic albino rats Ind. J. Physiol. Pharmacol. 33(2), 97–100.

    CAS  Google Scholar 

  21. Shibib, B.A., Khan, L.A. and Rahman, R. (1993) Hypoglycaemic activity ofCoccinia indica andMomordica charantia in diabetic rats, depression of hepatic gluconeogenic enzymes glucose-6-phosphatase and fructose-1,6-bisphophatase and elevation of both liver and red cell shunt enzyme glu-6-phosphate dehydrogenase. Biochem. J. 291(1), 267–270.

    Google Scholar 

  22. Sharma, R.D. (1986) Effect of fenugreek seeds and leaves on blood glucose and serum insulin response in human subjects. Nutr. Res. 6, 1353–1364.

    Article  Google Scholar 

  23. Stark, A. and Madar, Z. (1993) The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile and absorption and cholesterol levels in rats. Brit. J. Nutri. 69, 277–287.

    Article  CAS  Google Scholar 

  24. Khosla, P., Gupta, D.D. and Nagpal, R.K. (1995) Effect ofTrigonella foenum graecum (fenugreek) on blood glucose in normal and diabetic rats. Ind. J. Physiol. Pharmacol. 39(2), 173–174. and protein phosphotyrosine phosphatase. Mol. Cell. Biochem. 153, 39–47.

    CAS  Google Scholar 

  25. Pugazhenthi, S and Murthy, P.S. (1989) Studies on the isolation and effect of three orally active hypoglycemic principles Kakara Ib, IIIa and IIIb from bitter gourd (Momordica charantia Linn.) Diabetes Bulletin, 9, 73–76.

    Google Scholar 

  26. Pugazhenthi, S. and Murthy, P.S. (1995) Partial purification of a hypoglycemic fraction from the unripe fruit ofMomordica charantia (bitter gourd) Ind. J. Clin Biochem, 10(1), 19–22. b) Pugazhenthi, S. and Murthy P.S. (1996) Purification of three orally active hypoglycemic compounds Kakara Ib, IIIa and III b1 from the unripe fruits ofMomordica charantia Linn (bitter gourd) Ind. J. Clin. Biochem. 11(2), 115–119

    Google Scholar 

  27. Murthy, P.S. (1995) Potential of medicinal plants for the treatment of diabetes mellitus and other diseases Ind. J. Clin. Biochem. 10(2), 52–53. b) Moorthy, R., Prabhu, K.M. and Murthy, P.S. (1989) Studies on the isolation and effect of an orally active hypoglycemic principle from the seeds of fenugreek (Trigonella foenum graecum Diabetes Bulletin 9, 69–72. c) Puri, D., Prabhu, K.M., and Murthy, P.S. (1994) Hypocholesterolemic effect of the hypoglycemic principle of fenugreek (Trigonella foenum graecum) seeds. Ind. J. Clin. Biochem. 9, 13–16.

    Article  Google Scholar 

  28. Heyliger, C.E., Tahihani, A.G. and McNeill, J.H. (1985) Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 227, 1474–1477.

    Article  PubMed  CAS  Google Scholar 

  29. Kaur, G., Singh, R. and Baquer, N.Z. (1981) Localization of gluconeogenic enzymes (glucose-6-phosphatase and frutose-1,6-bisphosphatase) in subcellular fractions from different regions of the rat brain. J. Bioscience 3, 125–128.

    Article  CAS  Google Scholar 

  30. Racker, E. (1951) The mechanism of action of glyoxalase I. J. Biol. Chem. 190, 685–696.

    PubMed  CAS  Google Scholar 

  31. Shecter, Y., Li, J., Meyerovitch, J., Gefel, D., Bruck, R., Elberg, G., Miller, D.S. and Shisheva, A. (1995) Insulin-like actions of vanadate are mediated in an insulin receptor independent manner, via nonreceptor protein tyrosine kinases and protein tyrosine phosphatases Mol. Cell. Biochem. 153, 39–47.

    Article  Google Scholar 

  32. Sekar, N., Li, J. and Shechter, Y. (1996) Vanadium salts as insulin substitutes: mechanisms of action a scientific and therapeutic tool in diabetes mellitus research. Crit. Rev. Biochem. Mol Biol. 31, 339–359.

    Article  PubMed  CAS  Google Scholar 

  33. Kinoshita, J.H., Fukushi, S., Kador, P. and Manola, L.O. (1979) Aldose reductase inhibitors in diabetic complications of the eye metabolism. Metabolism 28, 462–469.

    Article  PubMed  CAS  Google Scholar 

  34. Gonzalez, A.M., Sochor, M., Hothersall, J.S. and McLean, P. (1986) Effect of aldose reductase inhibitor on integration of polyol pathway and glycolytic route in diabetic rat lens. Diabetes, 35, 1200–1205.

    Article  PubMed  CAS  Google Scholar 

  35. Srivastava, S.K., Ansari, N., Nair, G.A., Jaspan, J., Rao, M.B. and Das, B. (1986) Hyperglycemia induced activation of human erythrocyte aldose reductase and alteration in kinetic properties. Biochim. Biophys. Acta 870, 302–311.

    PubMed  CAS  Google Scholar 

  36. Saxena, A.K., Srivastava, P. and Baquer, N.Z. (1992) Effects of vanadate on glycolytic enzymes and malic enzymes in insulin dependent and independent tissues of diabetic rats. Eur. J. Pharmacol. 216, 123–126.

    Article  PubMed  CAS  Google Scholar 

  37. Saxena, A.K., Srivastava, P., Kale, R.K. and Baquer, N.Z. (1993) Impaired antioxidant status in diabetic rat liver. Effect of vanadate. Biochem. Pharmacol. 45(3), 539–542.

    Article  PubMed  CAS  Google Scholar 

  38. Ramanadham, S., Mangold, J.J., Brownsey, R.W., Cros, G.H. and McNeil, J.H. (1989) Oral vanadyl sulfate in treatment of diabetes mellitus in rats. Am. J. Physiol. 257, H 904–911.

    Google Scholar 

  39. Ramasarma, T. (1996) Vanadium complexes with insulin mimic actions-A second line of protection against diabetes. Ind. J. Clin. Biochem. 11 (2), 92–107.

    CAS  Google Scholar 

  40. Brichard, M.S. and Henquin, J.C. (1995) The role of vanadium in the management of diabetes. Trends Pharmacol. Sci. 16, 265–270.

    Article  PubMed  CAS  Google Scholar 

  41. Sekar, N., Qian, S. and Shechter, Y. (1998) Vanadate elevates lipogenecity of starved rat adipose tissue: Mechanism of action. Endocrinology 139(5), 2514–2518.

    Article  PubMed  CAS  Google Scholar 

  42. Green, A. (1986) The insulin like effect of sodium vanadate on adipocytes: glucose transport is mediated at a post insulin receptor level. Biochem. J. 238, 663–669.

    PubMed  CAS  Google Scholar 

  43. Sochor, M., McLean, P., Brown, J. and Greenbaum, A.L. (1981) Regulation of pathway of ornithine metabolism. Effects of thyroid hormones and diabetes on the activity of enzymes at the ornithine cross roads in liver. Enzymes 26, 15–23.

    CAS  Google Scholar 

  44. Kazmi, S.M.I., Mayanil, C.S.K. and Baquer, N.Z. (1985) Malate-aspartate shuttle enzymes in rat regions, liver and heart during alloxan diabetes and insulin replacement. Enzymes 34, 98–106.

    CAS  Google Scholar 

  45. Salimuddin, Upadhyaya, K.C. and Baquer, N.Z. (1996) Effects of vanadate and insulin on the activities of selected enzymes of amino acid metabolism in alloxan diabetic rat kidney. Biochem. Mol. Biol. Int. 40(4), 853–860.

    PubMed  CAS  Google Scholar 

  46. Salimuddin, (1997) Ph. D. Thesis: Effect of vanadium salts on the expression of urea cycle and related enzymes during diabetes. School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.

    Google Scholar 

  47. Morris, S.M. Jr., Moncman, C.L., Rand, K.D., Dizides, G.J., Cederbaum, S.D. and O’Brien, W.E. (1987) Regulation of mRNA levels for five urea cycle enzymes in rat liver by diet, cyclic AMP and glucocorticoids. Arch. Biochem. Biophys. 256, 343–353.

    Article  PubMed  CAS  Google Scholar 

  48. Thormalley, P.J. (1993) Modification of the glyoxalase system in disease processes and prospects for therapeutic strategies. Biochem. Soc. Trans. 21, 531–534.

    Google Scholar 

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Correspondence to Najma Zaheer Baquer.

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Baquer, N.Z., Gupta, D. & Raju, J. Regulation of metabolic pathways in liver and kidney during experimental diabetes: Effects of antidiabetic compounds. Indian J Clin Biochem 13, 63–80 (1998). https://doi.org/10.1007/BF02867866

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