Ko Kuan-Yin, Wu Yen-Wen, Liu Cheng-Wei, Cheng Mei-Fang, Yen Ruoh-Fang, Yang Wei-Shiung
Department of Nuclear Medicine, National Taiwan University Hospital, Yunlin Branch, Yunlin County, Taiwan.
Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan.
Oncotarget. 2017 Sep 23;8(50):87795-87808. doi: 10.18632/oncotarget.21202. eCollection 2017 Oct 20.
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 F-FDG PET at week 8 (W8), W10, W12, W14, and W16. F-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.
目的是评估db/db小鼠心肌葡萄糖利用和左心室收缩功能的序贯变化。8只db/db小鼠和8只野生型小鼠在第8周（W8）、第10周、第12周、第14周和第16周接受了血浆底物分析和动态F-FDG PET检查。通过Patlak图像分析得出F-FDG摄取常数Ki和心肌葡萄糖摄取率（MRGlu）。另外8只db/db小鼠和8只野生型小鼠在W8、W12和W16接受了超声心动图检查，并测量了左心室结构和功能。随着年龄增长，db/db小鼠体重和血糖水平升高。与野生型相比，db/db小鼠的稳态模型评估估计胰岛素抵抗指数、胰岛素和游离脂肪酸浓度更高。db/db小鼠在所有时间点的MRGlu均明显高于野生型。在db/db小鼠中观察到MRGlu随年龄增长而升高。db/db小鼠的Ki和MRGlu与甘油三酯水平呈负相关。当将两组合并在一起时，Ki和MRGlu与血糖水平显著成比例。db/db小鼠和对照小鼠之间在左心室结构和功能方面未发现显著差异。总之，我们证明了db/db小鼠在左心室收缩功能障碍发作之前心肌葡萄糖利用发生了改变。
