Longitudinal evaluation of myocardial glucose metabolism and contractile function in obese type 2 diabetic db/db mice using small-animal dynamic (18)F-FDG PET and echocardiography

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 (18)F-FDG PET at week 8 (W8), W10, W12, W14, and W16. (18)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.