Download PDF

Diabetologia

, Volume 37, Issue 11, pp 1065–1072 | Cite as

Tissue-specific correction of lipogenic enzyme gene expression in diabetic rats given vanadate

  • S. M. Brichard
  • L. N. Ongemba
  • J. Girard
  • J. C. Henquin
Originals
Received:
Revised:

Summary

Vanadium is a potent insulinomimetic agent. In vivo, its blood glucose lowering action in insulin-deficient diabetic rats is associated with corrected expression of genes involved in hepatic glucose metabolism. In this study, we investigated whether vanadate treatment also reverses the impaired expression of genes coding for key enzymes of lipogenesis in diabetic liver and white adipose tissue. Oral administration of vanadate to streptozotocin-rats caused a 55% fall in plasma glucose levels after feeding without modifying low insulinaemia. It also partially corrected the low thyroid hormone concentrations. In untreated diabetic animals, hepatic mRNA levels of acetyl-CoA carboxylase and fatty acid synthase were reduced by more than 80 and 90%, respectively, in close correlation with changes in enzyme activities. Three weeks of vanadate treatment totally restored acetyl-CoA carboxylase mRNA and partially restored fatty acid synthase mRNA (71% of control levels). The activities of both lipogenic enzymes were increased 3.5 to 4-fold, to reach 45 to 65% of control values. By contrast, in white adipose tissue, vanadate modified neither expression nor activity of both lipogenic enzymes, which remained blunted (<10% of control levels). In conclusion, vanadate treatment partially restores the activities of two key lipogenic enzymes in liver, but not in white adipose tissue, of diabetic rats. This correction results from a reversal of impaired pre-translational regulatory mechanisms possibly mediated by an improvement of thyroid function and a selective restoration of liver glycolytic flux.

Key words

Vanadium lipogenic enzymes gene expression streptozotocin-diabetic rats 

Abbreviations

ACC

Acetyl-CoA carboxylase

FAS

fatty acid synthase

PEPCK

phosphoenolpyruvate carboxykinase

C

non-diabetic control rats

D

untreated diabetic rats

V

vanadate-treated diabetic rats

SSC

sodium saline citrate

SDS

sodium dodecyl sulphate

OD

optical density

kb

kilobase

Download to read the full article text

References

  1. 1.
    Mc Garry JD (1992) What if Minkowski had been ageusic? An alternative angle on diabetes. Science 258:766–770Google Scholar
  2. 2.
    Shechter Y (1990) Insulin mimetic effects of vanadate. Possible implications for future treatment of diabetes. Diabetes 39:1–5Google Scholar
  3. 3.
    Brichard SM, Lederer J, Henquin JC (1991) The insulin-like properties of vanadium: a curiosity or a perspective for the treatment of diabetes? Diabète Metab 17:435–440Google Scholar
  4. 4.
    Heyliger CE, Tahiliani AG, McNeill JH (1985) Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 227:1474–1477Google Scholar
  5. 5.
    Meyerovitch J, Farfel Z, Sack J, Shechter Y (1987) Oral administration of vanadate normalizes blood glucose levels in streptozotocin-treated rats. J Biol Chem 262:6658–6662Google Scholar
  6. 6.
    Gil J, Miralpeix M, Carreras J, Bartrons R (1988) Insulin-like effects of vanadate on glucokinase activity and fructose 2,6-bisphosphate levels in the liver of diabetic rats. J Biol Chem 263:1868–1871Google Scholar
  7. 7.
    Brichard SM, Okitolonda W, Henquin JC (1988) Long term improvement of glucose homeostasis by vanadate treatment in diabetic rats. Endocrinology 123:2048–2053Google Scholar
  8. 8.
    Blondel O, Bailbe D, Portha B (1989) In vivo insulin resistance in streptozotocin-diabetic rats — evidence for reversal following oral vanadate treatment. Diabetologia 32:185–190Google Scholar
  9. 9.
    Saxena AK, Srivastava P, Baquer NZ (1992) Effects of vanadate on glycolytic enzymes and malic enzyme in insulin-dependent and independent tissues of diabetic rats. Eur J Pharmacol 216:123–126Google Scholar
  10. 10.
    Cam MC, Pederson RA, Brownsey RW, McNeill JH (1993) Long-term effectiveness of oral vanadyl sulphate in streptozotocin-diabetic rats. Diabetologia 36:218–224Google Scholar
  11. 11.
    Pugazhenthi S, Angel JF, Khandelwal RL (1993) Effects of high sucrose diet on insulin-like effects of vanadate in diabetic rats. Mol Cell Biochem 122:77–84Google Scholar
  12. 12.
    Miralpeix M, Carballo E, Bartrons R, Crepin K, Hue L, Rousseau GG (1992) Oral administration of vanadate to diabetic rats restores liver 6-phosphofructo-2-kinase content and mRNA. Diabetologia 35:243–248Google Scholar
  13. 13.
    Brichard SM, Desbuquois B, Girard J (1993) Vanadate treatment of diabetic rats reverses the impaired expression of genes involved in hepatic glucose metabolism. Effects on glycolytic and gluconeogenic enzymes, and on glucose transporter GLUT 2. Mol Cell Endocrinol 91:91–97Google Scholar
  14. 14.
    Brichard SM, Pottier AM, Henquin JC (1989) Long term improvement of glucose homeostasis by vanadate in obese hyperinsulinemic fa/fa rats. Endocrinology 125:2510–2516Google Scholar
  15. 15.
    Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium-thiocyanate-phenolchloroform extraction. Anal Biochem 162:156–159Google Scholar
  16. 16.
    Sambrook J, Fritsch EF, Maniatis T (1989) Extraction, purification and analysis of messenger RNA from eukaryotic cells. In: Ford N, Nolan C, Fergusson M (eds) Molecular cloning. A laboratory manual, Vol 1. Cold spring harbor laboratory press, New York, p 7.22Google Scholar
  17. 17.
    Bai DH, Pape ME, Lopez-Casillas F, Luo XC, Dixon JE, Kim KH (1986) Molecular cloning of cDNA for acetyl-CoA carboxylase. J Biol Chem 261:12395–12399Google Scholar
  18. 18.
    Nepokroeff CM, Adachi K, Yan C, Porter JW (1984) Cloning of DNA complementary to rat liver fatty acid synthetase mRNA. Eur J Biochem 146:441–445Google Scholar
  19. 19.
    Yoo-Warren H, Monahan JE, Short J et al. (1983) Isolation and characterization of the gene coding for cytosolic phosphoenolpyruvate carboxykinase (GTP) from the rat. Proc Natl Acad Sci USA 80:3656–3660Google Scholar
  20. 20.
    Linn TC (1981) Purification and crystallization of rat liver fatty acid synthetase. Arch Biochem Biophys 209:613–619Google Scholar
  21. 21.
    Maeda H, Ikeda I, Sugano M (1975) Behavior of the liver key enzymes in rats fed threonine imbalanced diet. Nutr Rep Int 12:61–66Google Scholar
  22. 22.
    Chang HC, Lane MD (1966) The enzymatic carboxylation of phosphoenolpyruvate. II. Purification and properties of liver mitochondrial phosphoenolpyruvate carboxykinase. J Biol Chem 241:2413–2420Google Scholar
  23. 23.
    Bradford M (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254Google Scholar
  24. 24.
    Labarca C, Paigen K (1980) A simple, rapid, and sensitive DNA assay procedure. Anal Biochem 102:344–352Google Scholar
  25. 25.
    Sokal RR, Rohlf FJ (1969) Biometry. The principles and practice of statistics in biological research. Freeman, San Francisco, pp 1–776Google Scholar
  26. 26.
    Volpe JJ, Vagelos PR (1974) Regulation of mammalian fatty-acid synthetase.The roles of carbohydrate and insulin. Proc Natl Acad Sci USA 71:889–893Google Scholar
  27. 27.
    Volpe JJ, Marasa JC (1975) Hormonal regulation of fatty acid synthetase, acetyl-CoA carboxylase and fatty acid synthesis in mammalian adipose tissue and liver. Biochim Biophys Acta 380:454–472Google Scholar
  28. 28.
    Iritani N (1992) Nutritional and hormonal regulation of lipogenic-enzyme gene expression in rat liver. Eur J Biochem 205:433–442Google Scholar
  29. 29.
    Numa S, Nakanishi S, Hashimoto T, Iritani N, Okazaki T (1970) Role of acetyl-Coenzyme A carboxylase in the control of fatty acid synthesis. Vitam and Horm 28:213–243Google Scholar
  30. 30.
    Pape ME, Lopez-Casillas F, Kim KH (1988) Physiological regulation of acetyl-CoA carboxylase gene expression: effects of diet, diabetes, and lactation on acetyl-CoA carboxylase mRNA. Arch Biochem Biophys 267:104–109Google Scholar
  31. 31.
    Foufelle F, Gouhot B, Pégorier JP, Perdereau D, Girard J, Ferré P (1992) Glucose stimulation of lipogenic enzyme gene expression in cultured white adipose tissue. A role for glucose 6-phosphate. J Biol Chem 267:20543–20546Google Scholar
  32. 32.
    Katsurada A, Iritani N, Fukuda H, Matsumura Y, Nishimoto N, Noguchi T, Tanaka T (1990) Effects of nutrients and hormones on transcriptional and post-transcriptional regulation of acetyl-CoA carboxylase in rat liver. Eur J Biochem 190:435–441Google Scholar
  33. 33.
    Katsurada A, Iritani N, Fukuda H, Matsumura Y, Nishimoto N, Noguchi T, Tanaka T (1990) Effects of nutrients and hormones on transcriptional and post-transcriptional regulation of fatty acid synthase in rat liver. Eur J Biochem 190:427–433Google Scholar
  34. 34.
    Valera A, Rodriguez-Gil JE, Bosch F (1993) Vanadate treatment restores the expression of genes for key enzymes in the glucose and ketone bodies metabolism in the liver of diabetic rats. J Clin Invest 92:4–11Google Scholar
  35. 35.
    Begum N, Draznin B (1992) Effect of streptozotocin-induced diabetes on GLUT-4 phosphorylation in rat adipocytes. J Clin Invest 90:1254–1262Google Scholar
  36. 36.
    Moustaid N, Sul HS (1991) Regulation of expression of the fatty acid synthase gene in 3T3-L1 cells by differentiation and triiodothyronine. J Biol Chem 266:18550–18554Google Scholar
  37. 37.
    Stapleton SR, Mitchell DA, Salati LM, Goodridge AG (1990) Triiodothyronine stimulates transcription of the fatty acid synthase gene in chick embryo hepatocytes in culture. J Biol Chem 265:18442–18446Google Scholar
  38. 38.
    Fukuda H, Katsurada A, Iritani N (1992) Nutritional and hormonal regulation of mRNA levels of lipogenic enzymes in primary cultures of rat hepatocytes. J Biochem 111:25–30Google Scholar
  39. 39.
    Saunders J, Hall SEH, Sonksen PH (1978) Thyroid hormones in insulin requiring diabetes before and after treatment. Diabetologia 15:29–32Google Scholar
  40. 40.
    Sundaresan PR, Sharma VK, Gingold SI, Banerjee SP (1984) Decreased β-adrenergic receptors in rat heart in streptozotocin-induced diabetes: role of thyroid hormones. Endocrinology 114:1358–1363Google Scholar
  41. 41.
    Ramanadham S, Mongold JJ, Brownsey RW, Cros GH, McNeill JH (1989) Oral vanadyl sulfate in treatment of diabetes mellitus in rats. Am J Physiol 257:H904-H911Google Scholar
  42. 42.
    Oczelikay AT, Yildizoglu-Ari N, Ozuari A, Ozturk Y, Allan VM (1993) The effect of vanadate on altoxan-diabetic rat atria. Diabetes Res Clin Pr 19:189–194Google Scholar
  43. 43.
    Mayes PA (1993) Biosynthesis of fatty acids. In: Harper's Biochemistry. 23th edn. Appleton & Lange, Prentice Hall, East Norwalk, pp 212–219Google Scholar
  44. 44.
    Brichard SM, Henquin JC, Girard J (1993) Phlorizin treatment of diabetic rats partially reverses the abnormal expression of genes involved in hepatic glucose metabolism. Diabetologia 36:292–298Google Scholar
  45. 45.
    Agius L, Vaartjes WJ (1982) The effects of orthovanadate on fatty acid synthesis in isolated rat hepatocytes. Biochem J 202:791–794Google Scholar
  46. 46.
    Guzman M, Castro J (1990) Simultaneous stimulation of fatty acid synthesis and oxidation in rat hepatocytes by vanadate. Arch Biochem Biophys 283:90–95Google Scholar
  47. 47.
    Jackson TK, Salhanick AI, Sparks JD, Sparks CE, Bolognino M, Amatruda JM (1988) Insulin-mimetic effects of vanadate in primary cultures of rat hepatocytes. Diabetes 37:1234–1240Google Scholar
  48. 48.
    Duckworth WC, Solomon SS, Liepnicks J, Hamel FG, Hand S, Peavy DE (1988) Insulin-like effects of vanadate in isolated rat adipocytes. Endocrinology 122:2285–2289Google Scholar
  49. 49.
    Fantus IG, Ahmad F, Deragon G (1990) Vanadate augments insulin binding and prolongs insulin action in rat adipocytes. Endocrinology 127:2716–2725Google Scholar
  50. 50.
    Eriksson JW, Lönnroth P, Smith U (1992) Vanadate increases cell surface insulin binding and improves insulin sensitivity in both normal and insulin-resistant rat adipocytes. Diabetologia 35:510–516Google Scholar
  51. 51.
    Bosch F, Hatzoglou M, Park EA, Hanson RW (1990) Vanadate inhibits expression of the gene for phosphoenolpyruvate carboxykinase (GTP) in rat hepatoma cells. J Biol Chem 265:13677–13682Google Scholar
  52. 52.
    Lopez-Casillas F, Kim KH (1989) Heterogeneity at the 5' end of rat Acetyl-Coenzyme A carboxylase mRNA. Lipogenic conditions enhance synthesis of a unique mRNA in liver. J Biol Chem 264:7176–7184Google Scholar
  53. 53.
    Lopez-Casillas F, Ponce-Castaneda MV, Kim KH (1992) Acetyl-Coenzyme A carboxylase mRNA metabolism in the rat liver. Metabolism 41:201–207Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • S. M. Brichard
    • 1
  • L. N. Ongemba
    • 1
  • J. Girard
    • 2
  • J. C. Henquin
    • 1
  1. 1.Faculty of MedicineUnité d'Endocrinologie et Métabolisme, University of LouvainBrusselsBelgium
  2. 2.CNRSMeudonFrance

Personalised recommendations