Protective effects of mildronate in an experimental model of type 2 diabetes in Goto-Kakizaki rats
| Autor: | Reinis Vilskersts, Solveiga Grinberga, Liga Zvejniece, Ivars Kalvinsh, Baiba Svalbe, Elina Skapare, Janis Kuka, Helena Cirule, Edgars Liepinsh, Maija Dambrova |
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| Rok vydání: | 2009 |
| Předmět: |
Blood Glucose
Male Pain Threshold medicine.medical_specialty Myocardial Ischemia Administration Oral Type 2 diabetes In Vitro Techniques Diabetes Mellitus Experimental chemistry.chemical_compound Carnitine Internal medicine Diabetes mellitus medicine Animals Hypoglycemic Agents Rats Wistar Pharmacology chemistry.chemical_classification 3-Hydroxybutyric Acid business.industry Cardiovascular Agents Heart Metabolism medicine.disease Lipids Research Papers Rats Disease Models Animal Endocrinology Fructosamine Diabetes Mellitus Type 2 Mechanism of action chemistry Hyperalgesia Cardiovascular agent Propionate medicine.symptom business Methylhydrazines medicine.drug |
| Zdroj: | British Journal of Pharmacology. 157:1549-1556 |
| ISSN: | 1476-5381 0007-1188 |
| Popis: | Mildronate [3-(2,2,2-trimethylhydrazinium) propionate] is an anti-ischaemic drug whose mechanism of action is based on its inhibition of L-carnitine biosynthesis and uptake. As L-carnitine plays a pivotal role in the balanced metabolism of fatty acids and carbohydrates, this study was carried out to investigate whether long-term mildronate treatment could influence glucose levels and prevent diabetic complications in an experimental model of type 2 diabetes in Goto-Kakizaki (GK) rats.GK rats were treated orally with mildronate at doses of 100 and 200 mg.kg(-1) daily for 8 weeks. Plasma metabolites reflecting glucose and lipids, as well as fructosamine and beta-hydroxybutyrate, were assessed. L-carnitine concentrations were measured by ultra performance liquid chromatography with tandem mass spectrometry. An isolated rat heart ischaemia-reperfusion model was used to investigate possible cardioprotective effects. Pain sensitivity was measured with a tail-flick latency test.Mildronate treatment significantly decreased L-carnitine concentrations in rat plasma and gradually decreased both the fed- and fasted-state blood glucose. Mildronate strongly inhibited fructosamine accumulation and loss of pain sensitivity and also ameliorated the enhanced contractile responsiveness of GK rat aortic rings to phenylephrine. In addition, in mildronate-treated hearts, the necrosis zone following coronary occlusion was significantly decreased by 30%.These results demonstrate for the first time that in GK rats, an experimental model of type 2 diabetes, mildronate decreased L-carnitine contents and exhibited cardioprotective effects, decreased blood glucose concentrations and prevented the loss of pain sensitivity. These findings indicate that mildronate treatment could be beneficial in diabetes patients with cardiovascular problems. |
| Databáze: | OpenAIRE |
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