Protective effects of mildronate in an experimental model of type 2 diabetes in Goto-Kakizaki rats

British Journal of Pharmacology

Volumn 157, Issue 8, 2009, Pages 1549-1556

  Liepinsh, Edgars ^a   Vilskersts, Reinis ^a   Zvejniece, Liga ^a   Svalbe, Baiba ^a   Skapare, Elina ^a,b   Kuka, Janis ^a,b   Cirule, Helena ^a   Grinberga, Solveiga ^a   Kalvinsh, Ivars ^a   Dambrova, Maija ^a  

^a LATVIAN INSTITUTE OF ORGANIC SYNTHESIS   (Latvia)

^b RIGA STRADINS UNIVERSITY   (Latvia)

Author keywords

Diabetes; Glucose; Goto Kakizaki rat; L carnitine; Mildronate; Myocardial infarction; Pain sensitivity

Indexed keywords

3 HYDROXYBUTYRIC ACID; CARNITINE; FATTY ACID; GLUCOSE; INSULIN; MILDRONATE; PHENYLEPHRINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DISEASE MODEL; DRUG MECHANISM; FATTY ACID OXIDATION; FRUCTOSAMINE BLOOD LEVEL; GLUCOSE BLOOD LEVEL; GOTO KAKIZAKI RAT; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HEART MUSCLE NECROSIS; HEART PROTECTION; LIPID BLOOD LEVEL; LIQUID CHROMATOGRAPHY; LONG TERM CARE; MALE; NOCICEPTION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PAIN ASSESSMENT; PRIORITY JOURNAL; RAT; REPERFUSION INJURY; TAIL FLICK TEST; TANDEM MASS SPECTROMETRY; VASCULAR RING;

3-HYDROXYBUTYRIC ACID; ADMINISTRATION, ORAL; ANIMALS; BLOOD GLUCOSE; CARDIOVASCULAR AGENTS; CARNITINE; DIABETES MELLITUS, EXPERIMENTAL; DIABETES MELLITUS, TYPE 2; DISEASE MODELS, ANIMAL; FRUCTOSAMINE; HEART; HYPERALGESIA; HYPOGLYCEMIC AGENTS; LIPIDS; MALE; METHYLHYDRAZINES; MYOCARDIAL ISCHEMIA; PAIN THRESHOLD; RATS; RATS, WISTAR;

EID: 70350324903     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2009.00319.x     Document Type: Article

References (29)

1. Azuma K, Toyofuku Y, Iesaki T, Otsuka A, Tanaka A, Mita T et al. (2006). Acarbose, an alpha-glucosidase inhibitor, improves endot-helial dysfunction in Goto-Kakizaki rats exhibiting repetitive blood glucose fluctuation. Biochem Biophys Res Commun 345: 688-693. (Pubitemid 43776986)
2. Bisbis S, Bailbe D, Tormo MA, Picarel-Blanchot F, Derouet M, Simon J et al. (1993). Insulin resistance in the GK rat: decreased receptor number but normal kinase activity in liver. Am J Physiol 265: E807-E813.
3. Broderick TL (2006). Hypocarnitinaemia induced by sodium pivalate in the rat is associated with left ventricular dysfunction and impaired energy metabolism. Drugs R D 7: 153-161.
4. Broderick TL, Quinney HA, Lopaschuk GD (1992). Carnitine stimulation of glucose oxidation in the fatty acid perfused isolated working rat heart. J Biol Chem 267: 3758-3763.
5. Choy CK, Rodgers JE, Nappi JM, Haines ST (2008). Type 2 diabetes mellitus and heart failure. Pharmacotherapy 28: 170-192.
6. Dambrova M, Cirule H, Svalbe B, Zvejniece L, Pugovichs O, Zorenko T et al. (2008). Effect of inhibiting carnitine biosynthesis on male rat sexual performance. Physiol Behav 95: 341-347.
7. Dambrova M, Liepinsh E, Kalvinsh I (2002). Mildronate: cardiopro-tective action through carnitine-lowering effect. Trends Cardiovasc Med 12: 275-279.
8. Foster DW (2004). The role of the carnitine system in human metabolism. Ann N Y Acad Sci 1033: 1-16.
9. Gauguier D, Froguel P, Parent V, Bernard C, Bihoreau MT, Portha B et al. (1996). Chromosomal mapping of genetic loci associated with non-insulin dependent diabetes in the GK rat. Nat Genet 12: 38-43. (Pubitemid 26011317)
10. Gonzalez-Ortiz M, Hernandez-Gonzalez SO, Hernandez-Salazar E, Martinez-Abundis E (2008). Effect of oral L-carnitine administration on insulin sensitivity and lipid profile in type 2 diabetes mellitus patients. Ann Nutr Metab 52: 335-338.
11. Hayashi Y, Kirimoto T, Asaka N, Nakano M, Tajima K, Miyake H et al. (2000). Beneficial effects of MET-88, a gamma-butyrobetaine hydroxylase inhibitor in rats with heart failure following myocar-dial infarction. Eur J Pharmacol 395: 217-224.
12. Kuwajima M, Fujihara H, Sei H, Umehara A, Sei M, Tsuda TT et al. (2007). Reduced carnitine level causes death from hypoglycemia: possible involvement of suppression of hypothalamic orexin expression during weaning period. Endocr J 54: 911-925.
13. Liepinsh E, Vilskersts R, Loca D, Kirjanova O, Pugovichs O, Kalvinsh I et al. (2006). Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardio-protection in isolated rat heart infarction. J Cardiovasc Pharmacol 48: 314-319.
14. Liepinsh E, Vilskersts R, Skapare E, Svalbe B, Kuka J, Cirule H et al. (2008). Mildronate decreases carnitine availability and up-regulates glucose uptake and related gene expression in the mouse heart. Life Sci 83: 613-619.
15. Malone JI, Cuthbertson DD, Malone MA, Schocken DD (2006). Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats. Cardiovasc Diabetol 5: 2-7.
16. Malone JI, Schocken DD, Morrison AD, Gilbert-Barness E (1999). Diabetic cardiomyopathy and carnitine deficiency. J Diabetes Complications 13: 86-90.
17. Mingrone G (2004). Carnitine in type 2 diabetes. Ann N Y Acad Sci 1033: 99-107.
18. Rosen P, Wiernsperger NF (2006). Metformin delays the manifestation of diabetes and vascular dysfunction in Goto-Kakizaki rats by reduction of mitochondrial oxidative stress. Diabetes Metab Res Rev 22: 323-330.
19. Sena CM, Nunes E, Louro T, Proenca T, Fernandes R, Boarder MR et al. (2008). Effects of alpha-lipoic acid on endothelial function in aged diabetic and high-fat fed rats. Br J Pharmacol 153: 894-906.
20. Sesti C, Simkhovich BZ, Kalvinsh I, Kloner RA (2006). Mildronate, a novel fatty acid oxidation inhibitor and antianginal agent, reduces myocardial infarct size without affecting hemodynamics. J Cardio-vasc Pharmacol 47: 493-499.
21. Spaniol M, Brooks H, Auer L, Zimmermann A, Solioz M, Stieger B et al. (2001). Development and characterization of an animal model of carnitine deficiency. Eur J Biochem 268: 1876-1887.
22. Statsenko ME, Belenkova SV, Sporova OE, Shilina NN (2007). The use of mildronate in combined therapy of postinfarction chronic heart failure in patients with type 2 diabetes mellitus. Klin Med (Mosk) 85: 39-42.
23. Stephens FB, Constantin-Teodosiu D, Greenhaff PL (2007). New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle. J Physiol 581: 431-444.
24. Suzuki K, Yen-Chung H, Toyota T, Goto Y, Hirata Y, Okada K (1990). The significance of nerve sugar levels for the peripheral nerve impairment of spontaneously diabetic GK (Goto-Kakizaki) rats. Diabetes Res 14: 21-25.
25. Taegtmeyer H, McNulty P, Young ME (2002). Adaptation and malad-aptation of the heart in diabetes: Part I: general concepts. Circulation 105: 1727-1733. (Pubitemid 34298619)
26. Ueta K, Ishihara T, Matsumoto Y, Oku A, Nawano M, Fujita T et al. (2005). Long-term treatment with the Na+-glucose cotransporter inhibitor T-1095 causes sustained improvement in hyperglycemia and prevents diabetic neuropathy in Goto-Kakizaki Rats. Life Sci 76: 2655-2668.
27. Uziel G, Garavaglia B, Di DS (1988). Carnitine stimulation of pyruvate dehydrogenase complex (PDHC) in isolated human skeletal muscle mitochondria. Muscle Nerve 11: 720-724.
28. van Knegsel AT, van den Brand H, Dijkstra J, Tamminga S, Kemp B (2005). Effect of dietary energy source on energy balance, production, metabolic disorders and reproduction in lactating dairy cattle. Reprod Nutr Dev 45: 665-688.
29. Zaugg CE, Spaniol M, Kaufmann P, Bellahcene M, Barbosa V, Tolnay M et al. (2003). Myocardial function and energy metabolism in carnitine-deficient rats. Cell Mol Life Sci 60: 767-775.