Longitudinal evaluation of myocardial glucose metabolism and contractile function in obese type 2 diabetic db/db mice using small-animal dynamic 18F-FDG PET and echocardiography
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Kuan-Yin Ko1,2,8, Yen-Wen Wu2,3,4,5,6, Cheng-Wei Liu5,7,8, Mei-Fang Cheng2,9, Ruoh-Fang Yen2 and Wei-Shiung Yang3,8,10,11
1Department of Nuclear Medicine, National Taiwan University Hospital, Yunlin Branch, Yunlin County, Taiwan
2Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan
3Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan
4National Yang-Ming University School of Medicine, Taipei, Taiwan
5Cardiology Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan
6Department of Nuclear Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
7Department of Internal Medicine, Tri-Service General Hospital, Songshan Branch, National Defense Medical Center, Taipei, Taiwan
8Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
9Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, Taipei, Taiwan
10Department of Medicine and Graduate Institute of Medical Genomics & Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan
11R & D Branch Office, College of Medicine, National Taiwan University, Taipei, Taiwan
Yen-Wen Wu, email: [email protected]
Keywords: type 2 diabetes mellitus (DM), db/db mice, small animal imaging, positron emission tomography (PET), 18F-fluorodeoxyglucose (18F-FDG)
Received: June 22, 2017 Accepted: August 17, 2017 Published: September 23, 2017
The aim was to evaluate sequential changes of myocardial glucose utilization and LV systolic function in db/db mice.
Eight db/db and eight wild-type mice underwent plasma substrate analysis and dynamic 18F-FDG PET at week 8 (W8), W10, W12, W14, and W16. 18F-FDG uptake constant Ki and the rate of myocardial glucose uptake (MRGlu) were derived via Patlak graphic analysis. Another 8 db/db and 8 wild-type mice received echocardiography at W8, W12, and W16 and LV structure and function were measured.
The db/db mice showed increased weights and glucose levels as they aged. The index of homeostasis model assessment-estimated insulin resistance, insulin, and free fatty acid concentrations were higher in db/db mice compared with wild-type. MRGlu of db/db mice across all time points was markedly higher than that of wild-type. An age-dependent elevation of MRGlu was observed in db/db mice. Ki and MRGlu of db/db mice showed negative correlation with triglyceride levels. When two groups were pooled together, Ki and MRGlu were significantly proportional to glucose levels. No significant difference in LV structure and function was noted between db/db and control mice.
In conclusion, we demonstrated altered myocardial glucose utilization preceding the onset of LV systolic dysfunction in db/db mice.
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