期刊
CIRCULATION-CARDIOVASCULAR IMAGING
卷 2, 期 5, 页码 373-381出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCIMAGING.108.843227
关键词
metabolic imaging; type 2 diabetes; gene expression; response to therapy
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL013851] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK056341] Funding Source: NIH RePORTER
- NHLBI NIH HHS [P01 HL013851, P01 HL013851-44, 2P01HL13851] Funding Source: Medline
- NIDDK NIH HHS [P30 DK056341-09, P30 DK56341, P30 DK056341-08, P30 DK056341] Funding Source: Medline
Background-Cardiovascular disease is the leading cause of death among diabetic patients, with alteration in myocardial substrate metabolism being a likely contributor. We aimed to assess noninvasively the efficacy of metformin and rosiglitazone monotherapy in normalizing myocardial substrate metabolism in an animal model of type 2 diabetes mellitus. Methods and Results-The study used 18 male ZDF rats (fa/fa) with 6 rats in each group: an untreated group; a group treated with metformin (16.6 mg/kg/d), and a group treated with rosiglitazone (4 mg/kg). Each rat was scanned at age 14 weeks ( baseline) and subsequently at 19 weeks with small-animal positron emission tomography to estimate myocardial glucose utilization (MGU) and myocardial utilization (MFAU), oxidation (MFAO), and esterification (MFAE). Treatment lasted for 5 weeks after baseline imaging. At week 19, rats were euthanized and hearts were extracted for expression analysis of select genes encoding for GLUT transporters and fatty acid transport and oxidation genes. In addition, echocardiography measurements were obtained at weeks 13 and 18 to characterize cardiac function. Metformin had no significant effect on either MGU or MFAU and MFAO. In contrast, rosiglitazone tended to enhance MGU and significantly reduced MFAU and MFAO. Rosiglitazone-induced increase in glucose uptake correlated significantly with increased expression of GLUT4, whereas diminished MFAO correlated significantly with decreased expression of FATP-1 and MCAD. Finally, changes in fractional shortening as a measure of cardiac function were unchanged throughout the study. Conclusions-Treatment with rosiglitazone enhanced glucose utilization and diminished MFAO, thus reversing the metabolic phenotype of the diabetic heart. (Circ Cardiovasc Imaging. 2009;2:373-381.)
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