Duygu ŞAHİN, Nilgün ALTAN, Aylin SEPİCİ-DİNÇEL, Atilla ENGİN

The Effects of Thyroid Hormones on Glucokinase Enzyme Activity in diabetic Rat Liver Tissues

Objective: We aimed to investigate the effcts of insulin and various doses of thyroid hormones with combine treatment on glucokinase (GK) enzyme activity, which is the one of the key enzyme in carbohydrate metabolism, diabetes and hypothyroidism. Material and methods: Rats were assigned to eight groups: Group 1: control, Group 2: diabetes (DM), Group 3: DM + insulin, Group 4: thyroidectomized control, Group 5: thyroidectomized + DM, Group 6: thyroidectomized + DM + insulin, Group 7: thyroidectomized + DM + insulin + thyroid hormone (TH) (2.5μg/kg), Group 8: thyroidectomized + DM + insulin + TH (5 μg/kg). Glucose concentration, HbA1c and thyroid hormone levels were measured in blood samples and GK enzyme activities were determined in liver tissue samples.Results: Our results showed that the glucokinase enzyme activities were significantly decreased in diabetic rat liver tissues compared to control group. Moreover it was observed that the enzyme activities were slightly regulated by insulin. It is demonstrated that decreased GK enzyme activity in thyroidectomized diabetic rat liver was regulated by insulin and various doses of thyroid hormones.Conclusion: As a result the possible contribution of thyroid hormones to insulin effct to normalize diabetic induced changes in liver tissue has been shown.

Anahtar Kelimeler:

Glucokinase, Thyroid hormone, Diabetes Mellitus, Rat liver

PDF

___

1. American Diabetes Association, Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2006;29 (Suppl 1):43-48.
2. Magnuson MA. Glucokinase gene structure: functional implications of molecular genetic studies. Diabetes 1990;39:523-27.
3. Iynedjian PB, Gjinovci A, Renold AE. Stimulation by insulin of glucokinase gene transcription in liver of diabetic rats. J Biol Che 1988;263(2):740-4.
4. Magnuson MA, Andreone TL, Printz RL, et al. Rat glucokinase gene: structure and regulation by insulin. Proc Natl Acad Sci 1989;86:4838-42.
5. Iynedjian PB, Jotterand D, Nouspikel T, et al. Transcriptional induction of glucokinase gene by insulin in cultured liver cells and its repression by the glucagon-cAMP system. J Biol Chem 1989;264(36):21824-9.
6. Sibrowski W, Seitz HJ. Hepatic glucokinase turnover in intact and adrenalectomized rats in vivo. Eur J Biochem 1980;113(1):121-9.
7. Postic C, Shiota M, Niswender KD, et al. Dual Roles for Glucokinase Homeostasis as Determined by Liver and Pancreatic β cell-specific Gene Knock-outs Using Cre Recombinase. The Journal of Biological Chemistry 1999;274(1):305-315.
8. Aiston S, Trinh KY, Lange AJ, et al. Glucose- 6-phosphatase Overexpression Lowers Glucose 6-phosphate and Inhibits Glycogen Synthesis and Glycolysis in Hepatocytes without Affcting Glucokinase Translocation. The Journal of Biological Chemistry 1999;274(35):24559-24566.
9. Decaux, JF, Juanes M, Bossard P, Girard J. Effcts of triiodothyronine and retinoic acid on glucokinase gene expression in neonatal rat hepatocytes, Mol. Cell. Endocrinol 1997;130(1-2), 61-7.
10. Takiguchi Y, Satoh N, Hashimoto H, Nakashima M. Reversal Effct of Thyroxine on Altered Vascular Reactivity in Diabetic Rats. J. Cardiovasc. Pharmac 1984;13:520-24.
11. Karasu C, Ozturk Y, Altan N, et al. Thyroid hormones mediated effct of insulin on alloxan diabetic rat atria. Gen Pharmacol 1990;21:735-40.
12. Postic C, Shiota M, Magnuson MA. Cell-specific roles of glucokinase in glucose homeostasis. Recent Prog Horm Res 2001;56:195-217.
13. Hoppner W, Seitz NJ. Effct of Thyroid Hormones on Glucokinase Gene Transcription in Rat Liver. The Journal of Biological Chemistry 1989;264(34):20643-7.
14. Koh H, Tsushima M, Harano Y. Effct of Carbohydrate intake on serum 3,5,3’ Triiodothyronine response to glucose ingestion and its relation to glucose tolerance in lean non-insulin dependent diabetic patients. Arzneim-Forsch./Drug Res 1999;49(1):30-34.
15. Sutherland VL, McReynolds M, Tompkins LS, et al. Developmental expression of glucokinase in rat hypothalamus. Developmental Brain Research 2005; 154: 255-258.
16. Magnuson MA, Nikodem VM. Molecular cloning of a cDNA sequence for rat malic enzyme. Direct evidence for induction in vivo of rat liver malic enzyme mRNA by thyroid hormone. J Biol Chem 1983;258(20):12712-7.
17. Dozin B, Magnuson MA, Nikodem VM. Tissue-specific regulation of two functional malic enzyme mRNAs by triiodothyronine. Biochemistry 1985;24(20):5581-6.
18. Dozin B, Magnuson MA, Nikodem VM. Thyroid hormone regulation of malic enzyme synthesis. Dual tissue-specific control. J Biol Chem 1986;261(22):10290-2.
19. Siddiqui UA, Goldflm T, Goodridge AG. Nutritional and hormonal regulation of the translatable levels of malic enzyme and albumin mRNAs in avian liver cells in vivo and in culture. J Biol Chem 1981;256(9):4544-50.
20. Walker DG, Parry MJ. Glucokinase. In: Wood, W.A. (Ed.) Methods in Enzymology, Academic Press, New York,1966;9:381-388.
21. Di Pietro LD, Wienhouse S. Hepatic glucokinase in the fed, fasted and alloxan-diabetic rats. The Journal of Biological Chemistry 1960;235:2542- 2545.
22. Lowry OH. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265-275.
23. Kosova F, Sepici-Dincel A, Engin A, et al. The thyroid hormone mediated effcts of insulin on serum leptin levels of diabetic rats. Endocrine 2009;33(3):317-322.
24. Ferre T, Riu E, Bosch F, Valera A. Evidence from transgenic mice that glucokinase is rate limiting for glucose utilization in the liver. FASEB J 1996;10:1213-8.