Therapeutic association of atorvastatin and insulin in cardiac ischemia: Study in a model of type 2 diabetes with hyperlipidemia
| Autor: | A. R. Moedas, Luís A Providência, Lino Gonçalves, Elsa Nunes, Paulo Matafome, Pedro Monteiro, T. Louro, C. Amaral, Raquel Seiça |
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| Rok vydání: | 2008 |
| Předmět: |
Blood Glucose
medicine.medical_specialty medicine.medical_treatment Atorvastatin Hyperlipidemias Type 2 diabetes In Vitro Techniques Mitochondria Heart Eating Insulin resistance Diabetes mellitus Internal medicine Hyperlipidemia medicine Animals Hypoglycemic Agents Insulin Pyrroles Triglycerides Inflammation Pharmacology Adiponectin medicine.diagnostic_test business.industry Body Weight nutritional and metabolic diseases Drug Synergism medicine.disease Dietary Fats Lipids Rats Perfusion Oxidative Stress Cholesterol Endocrinology Diabetes Mellitus Type 2 Heptanoic Acids lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors Insulin Resistance Mitochondrial Swelling Lipid profile business Biomarkers medicine.drug |
| Zdroj: | Pharmacological Research. 58:208-214 |
| ISSN: | 1043-6618 |
| DOI: | 10.1016/j.phrs.2008.07.005 |
| Popis: | Combination therapy recently emerged as a potential therapeutic option in order to improve cardiovascular risk in diabetics, since therapies commonly used in monotherapy failed in significantly optimizing this risk. Methods: A type 2 diabetes animal model was used to test the effects of a high-fat diet, atorvastatin and insulin (isolated or in association), in glycemic, lipid and inflammatory profiles, oxidative stress markers and cardiac mitochondrial function in ischemia–reperfusion conditions. Results: High-fat diets significantly worsened fasting glycemia and lipid profile; it also increased C-reactive protein (CRP) and oxidative stress and compromised mitochondrial response to ischemia. Insulin decreased fasting glucose and free fatty acid levels and insulin resistance, while increasing HDL–cholesterol, but had no effect in inflammatory markers. Atorvastatin decreased circulating adiponectin levels and did not improve inflammatory markers, although it improved fasting glycemia, glucose tolerance, free fatty acids and HDL–cholesterol. The combined use of atorvastatin and insulin improved several parameters, as did each of the treatments separately. However, treatment association went beyond these results, by decreasing atherogenicity index and circulating CRP levels. Insulin and its association with atorvastatin significantly prevented mitochondrial dysfunction observed in the high-fat diet group, while atorvastatin showed some beneficial effects but in much less extent. Conclusions: Altogether, these results show that administration of an high-fat diet in a model of type 2 diabetes increases cardiovascular risk and combined use of atorvastatin and insulin provides a superior control of cardiovascular risk markers in diabetic and hyperlipidemic subjects. |
| Databáze: | OpenAIRE |
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