Primary AppointmentAssistant Professor, Radiology
Evaluation of glucose metabolism, using Positron Emission Tomography (PET), in murine models of LVH and type 2 diabetes mellitus (T2DM).
Metabolic Remodeling in Left Ventricular Hypertrophy: Systemic hypertension or aortic valve stenosis can lead to LVH, which is associated with early death and disability from cardiovascular disease. Myocardial hypertrophy is considered initially an adaptive response to stress. With ongoing stress, hypertrophy becomes maladaptive. Hypertrophy and ensuing heart failure are accompanied by changes in energy substrate metabolism which may result in decreased ATP production. During myocardial hypertrophy, there is a shift away from fatty-acid oxidation to glucose metabolism. Based on earlier work from the laboratory, we proposed that this metabolic remodeling precedes LV remodeling in pressure overload LVH and induces the fetal gene program. However, this hypothesis has not been validated in-vivo. The mouse model of pressure overload after transverse aortic constriction (TAC) is a clinically relevant model to assess metabolism, structure and function of the stressed heart in a serial fashion. We propose that identifying metabolic change during LVH and progression to heart failure is now possible because of advances in non-invasive imaging of mouse hearts with small animal scanners. We have developed quantitative glucose transport models with spill-over and partial volume corrections to accurately estimate rates of myocardial glucose influx in normal hearts and hearts subjected to pressure overload LVH.
In-Vivo Imaging of Tissue Glucose Metabolism in Type 2 Diabetes: In this project we describe the use of PET with 18F-2fluoro-2-deoxy-D-glucose (FDG) along with Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) imaging for quantitative evaluation of glucose metabolism in tissues. Insulin resistance is defined as decreased glucose tissue uptake and metabolism in response to insulin and is a hallmark of type II diabetes mellitus (T2DM). Glucose tolerance tests (GTTs) can be performed on serial blood samples to measure the kinetics of whole animal glucose disposal, but GTTs do not provide non-invasive information about tissue glucose uptake, i.e. in the myocardium, liver and skeletal muscle. FDG transport in a compartmental model enables us to measure blood and tissue glucose levels in-vivo and perform serial measurements without sacrificing the animals. Although it is known that glucose disposal is inhibited in T2DM, the kinetics of tissue redistribution associated with T2DM and potential treatments are not clear.