Abstract
1092
Objectives GK rats are non-obese with an early onset of T2DM at the age of 2 weeks. The goal of this study was to characterize alterations in myocardial substrate metabolism in both male and female GK rats over a 10week period.
Methods The study utilized 10 GK rats and 10 Wistar rats as controls with five rats per gender for a total of four groups. Each rat was imaged at 9 weeks (9W) and again at 19 weeks (19W) of age with small animal PET and three tracers in series: [11C]Acetate to quantify blood flow (MBF), [11C]Palmitate to quantify fatty acid metabolism, and FDG to quantify glucose metabolism. Blood samples were obtained during imaging protocol to determine concentration of insulin, glucose, fatty acid, triglycerides as well as glycated hemoglobin (HbA1C). Myocardial substrate metabolism was quantified based on established techniques to obtain estimates of MBF, myocardial fatty acid oxidation (MFAO) and uptake rate (MFAOUpR), myocardial fatty acid utilization (MFAU) and uptake rate (MFAUUpR) as well as myocardial glucose utilization (MGU). In addition, echocardiography (ECHO) measurements were obtained at both time-points to characterize changes in cardiac function as well as to facilitate partial-volume corrections based on established methods. Differences in measures were evaluated by two-way ANOVA. A P value of P<0.05 was considered statistically significant.
Results At 9W, both male and female GK rats exhibited significantly lower MGU than control rats. No significant differences in fatty acid oxidation measures were observed. At 19W, in addition to differences in MGU observed at 9W, female GK rats exhibited significantly higher MFAO and MFAU than control rats, although gender-differences were not significant.
Conclusions While both male and female GK rats are insulin-resistant at 9W, by 19W female GK rats utilize fatty acids significantly more than controls.
Research Support NIH/NIBIB 1R01EB01228