EFFECT OF COMBINED NICOTINAMIDE, ACETYL-L-CARNITINE AND α-LIPOIC ACID ACTION ON SEPARATE LINKS OF CARBOHYDRATE METABOLISM UNDER EXPERIMENTAL TYPE 2 DIABETES
DOI: http://dx.doi.org/10.30970/sbi.0803.391
Abstract
The effect of nicotinamide, acetyl-L-carnitine and α-lipoic acid on the separate links of carbohydrate metabolism in the brain, heart and liver of rats for type 2 diabetes it was investigated. Combined administration of nicotinamide, acetyl-L-carnitine and α-lipoic acid caused partial reduction of hyperglycemia in rats. By the action of investigated compounds activity of hexokinase and glucokinase, which were reduced under diabetes by 62 and 84 %, respectively, as compared to control was partially normalized. NAD contents in brain, heart and liver of diabetic rats were decreased by 46, 52 and 36 %, but were elevated by investigated compounds, especially in liver. It was found that ratio of free NAD/NADH and NADP/NADPH couples under diabetes were decreased in brain, liver and heart as compared to control. Redox-states in these tissues were significantly normalized by investigated compounds. Amino acid concentrations in blood serum of rats were altered and partially normalized by investigated compounds. Thus, combined effect of investigated compounds is more effective and can be used for the correction of carbohydrate metabolism and energetic state that were changed under type 2 diabetes.
Keywords
Full Text:
PDF (Українська)References
1. Agius L. Glucokinase and molecular aspects of liver glycogen metabolism. Biochemical Journal, 2008; 414(1): 1-18. | |
| |
2. Bak J., Pedersen O. Glycogen synthase: characteristics and putative role in insulin insensitivity. Diabetes Annals, 1994; 8: 75-105. | |
| |
3. Bergmeyer H. Methods of Enzymatic Analysis. New York, London: Verlag Chemie, 1963. - 2300 p. | |
| |
4. Bouché C., Serdy S., Kahn C. R. et al. The cellular fate of glucose and its relevance in type 2 diabetes. Endocrine Reviews, 2004; 25(5): 807-830. | |
| |
5. Coleman M.D., Eason R.C., Bailey C.I. The therapeutic use of lipoic acid in diabetes: a current perspective. Enviroment Toxicology Pharmacology, 2001; 10: 167-173. | |
| |
6. Coughlan K. A., Valentine R. J., Ruderman N. B. AMPK activation: a therapeutic target for type 2 diabetes? Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2014; 7: 241-253. | |
| |
7. Danforth W. H. Glycogen synthetase activity in skeletal muscle. The Journal of Biological Chemistry, 1965; 240(2): 588-593. | |
| |
8. Delarue J., Magnan C. Free fatty acids and insulin resistance. Current Opinion in Clinical Nutrution and Metabolic Care, 2007; 10(2): 142-148. | |
| |
9. Drel V.R., Pacher P., Stavniichuk R. et al. Poly(ADP-ribose)polymerase inhibition counteracts renal hypertrophy and multiple manifestations of peripheral neuropathy in diabetic Akita mice. International Journal of Molecular Medicine, 2011; 4(28): 629-635. | |
| |
10. Eprinsev A.T., Shevchenko M.Yu., Popov V.N. Carbohydrate metabolism in the liver of rats in food deprivation and experimental diabetes. Biology Bulletins, 2008; 35(1): 99-101. | |
| |
11. Fahien L., MacDonald J. M. The succinate mechanism of insulin release. Diabetes, 2002; 51: 2669-2676. | |
| |
12. Ferrero E., Buono N. L., Horenstein A. L. et al. The ADP-ribosyl cyclases - the current evolutionary state of the ARCs. Frontiers in Bioscience, 2014; 19: 986-1002. | |
| |
13. Forbes J. M., Cooper M. E. Mechanisms of diabetic complications. Physiology Reviews, 2013; 93: 137-188. | |
| |
14. Giacco F., Brownlee M. Oxidative stress and diabetic complications. Circulation Research, 2010; 107: 1058-1070. | |
| |
15. Guse A. H. Biochemistry, biology, and pharmacology of cyclic adenosine diphosphoribose (cADPR). Current Medical Chemistry, 2004; 11(7): 847-855. | |
| |
16. Hemmings S.J., Spafford D. Neonatal STZ model of type II diabetes mellitus in the Fischer 344 rat: characteristics and assessment of the status of the hepatic adrenergic receptors. The International Journal of Biochemistry & Cell Biology, 2000; 32: 905-919. | |
| |
17. Imai S., Kiess W. Therapeutic potential of SIRT1 and NAMPT-mediated NAD biosynthesis in type 2 diabetes. Frontiers Bioscienсе (Landmark Ed), 2009; 14: 2983-2995. | |
| |
18. Kathirvel E., Kengathevy M., French S.W. et al. Acetyl-l-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease. Nutrition Research, 2013; 33(11): 932-941. | |
| |
19. Kuchmerovska Т., Shymanskyy I., Donchenko G. et al. Poly-ADP- ribosylation enhancement in brain cells nuclei is associated with diabetic neuropathy. Journal of Diabetes and Its Complications, 2004; 18(4):198-204. | |
| |
20. Lacroix I., Li-Chan E. Overview of food products and dietary constituents with antidiabetic properties and their putative mechanisms of action: A natural approach to complement pharmacotherapy in the management of diabetes. Molecular Nutrition & Food Research, 2014; 58(1): 61-78. | |
| |
21. Miyata Y., Shimomura I. Metabolic flexibility and carnitine flux: The role of carnitine acyltransferase in glucose homeostasis. Journal of Diabetes Investigation, 2013; 4(3): 247-249. | |
| |
22. Morifuji M., Sakai K., Sanbongi C. et al. Dietary whey protein increases liver and skeletal muscle glycogen levels in exercise-trained rats. British Journal of Nutrition, 2005; 93: 439-445. | |
| |
23. Moses R.G. Combination therapy for patients with type 2 diabetes: repaglinide in сombination with metformin. Expert Review of Endocrinology and Metabolism, 2010; 5(3): 331-342. | |
| |
24. Muecklera M., Thorens B. The SLC2 (GLUT) family of membrane transporters. Molecular Aspects of Medicine, 2013; 34(2-3): 121-138. | |
| |
25. Ribas G.S., Vargas C.R, Wajner M. L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders. Gene, 2014; 533(2): 469-476. | |
| |
26. Ringseis R., Keller J. Role of carnitine in the regulation of glucose homeostasis and insulin sensitivity: evidence from in vivo and in vitro studies with carnitine supplementation and carnitine deficiency. European Journal of Nutrition, 2012; 1: 1-18. | |
| |
27. Shaw J.E., Sicree R.A., Zimmet P.Z. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Research and Clinical Practice, 2010; 87: 4-14. | |
| |
28. Stahl W., Sies H. Antioxidant defence: Vitamins E and C and carothenoids. Diabetes, 1997; 46(2): 14-18. | |
| |
29. Thirunavukkarasu V., Nandhini A., Anuradha C.V. Lipoic acid improves glucose utilisation and prevents protein glycation and AGE formation. Pharmazie, 2005; 60(10): 772-775. | |
| |
30. Udupa A., Nahar P., Shah S. et al. A comparative study of effects of omega-3 fatty acids, alpha lipoic acid and vitamin E in type 2 diabetes mellitus. Annals of Medical and Health Science Research, 2013; 3: 442-446. | |
| |
31. Wilson J.E. Isozymes of mammalian hexokinase structure, subcellular localization and metabolic function. The Journal of Experimental Biology, 2003; 206: 2049-2057. | |
| |
32. Yanga S.J., Mook Choib J., Kim L. et al. Nicotinamide improves glucose metabolism and affects the hepatic NAD-sirtuin pathway in a rodent model of obesity and type 2 diabetes. The Journal of Nutritional Biochemistry, 2014; 25(1): 66-72. | |
| |
33. Ying W. NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxid Redox Signal, 2008; 10(2):179-206. | |
| |
34. Yoshino J., Mills K. F., Yoon M. J. et al. Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metabolism, 2011; 14(4): 528-536. | |
Refbacks
- There are currently no refbacks.
Copyright (c) 2014 Studia biologica
This work is licensed under a Creative Commons Attribution 4.0 International License.