| Acarbose reduces myocardial infarct size by preventing postprandial hyperglycemia and hydroxyl radical production and opening mitochondrial KATP channels in rabbits. | |
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MedLine Citation:
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PMID: 19487955 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Acarbose, an antidiabetic drug, is an alpha-glucosidase inhibitor that can inhibit glucose absorption in the intestine. A recent large-scale clinical trial, STOP-NIDDM, showed that acarbose reduces the risk of myocardial infarction. We examined whether acarbose reduces myocardial infarct size and investigated its mechanisms. METHODS AND RESULTS: Rabbits were fed with 1 of 2 diets in this study: normal chow, 30 mg acarbose per 100 g chow for 7 days. Rabbits were assigned randomly to 1 of 4 groups: control (n = 10), acarbose (n = 10), acarbose + 5HD (n = 10, intravenous 5 mg/kg of 5-hydroxydecanoate), and 5HD (n = 10, intravenous 5 mg/kg of 5HD). Rabbits then underwent 30 minutes of coronary occlusion followed by 48-hour reperfusion. Postprandial blood glucose levels were higher in the control group than in the acarbose group. The infarct size as a percentage of the left ventricular area at risk was reduced significantly in the acarbose (19.4% +/- 2.3%) compared with the control groups (42.8% +/- 5.4%). The infarct size-reducing effect of acarbose was abolished by 5HD (43.4% +/- 4.7%). Myocardial interstitial 2,5-dihydroxybenzoic acid levels, an indicator of hydroxyl radicals, increased during reperfusion after 30 minutes of ischemia, but this increase was inhibited in the acarbose group. This was reversed by 5HD. CONCLUSION: Acarbose reduces myocardial infarct size by opening mitochondrial KATP channels, which may be related to the prevention of postprandial hyperglycemia and hydroxyl radical production. |
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Authors:
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Shinya Minatoguchi; Zengi Zhang; Narentuoya Bao; Hiroyuki Kobayashi; Shinji Yasuda; Masamitsu Iwasa; Syouhei Sumi; Itta Kawamura; Yoshihisa Yamada; Kazuhiko Nishigaki; Genzou Takemura; Takako Fujiwara; Hisayoshi Fujiwara |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 54 ISSN: 1533-4023 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-07-21 Completed Date: 2009-12-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 25-30 Citation Subset: IM |
Affiliation:
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Second Department of Internal Medicine, Gifu University School of Medicine, Gifu 501-1194, Gifu 500, Japan. minatos@gifu-u.ac.jp |
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| MeSH Terms | |
Descriptor/Qualifier:
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Acarbose
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therapeutic use* Animals Blood Glucose / analysis Catechols / metabolism Enzyme Inhibitors / therapeutic use Gentisates / metabolism Hydroxybenzoic Acids / metabolism Hydroxyl Radical / metabolism* Hyperglycemia / drug therapy* Male Myocardial Infarction / drug therapy* Potassium Channels / metabolism* Rabbits |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Catechols; 0/Enzyme Inhibitors; 0/Gentisates; 0/Hydroxybenzoic Acids; 0/Potassium Channels; 0/mitochondrial K(ATP) channel; 120-80-9/catechol; 303-38-8/2-pyrocatechuic acid; 3352-57-6/Hydroxyl Radical; 490-79-9/2,5-dihydroxybenzoic acid; 56180-94-0/Acarbose |
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