(62ak) Novel Isotope Tracer Method for Quantifying Glucose Metabolism in Type-2 Diabetes

Accurately assessing in vivo rates of glucose turnover, gluconeogenesis, glycogen breakdown and futile cycling in the liver are crucial to understanding the control of whole-body glucose metabolism and how it becomes dysregulated in conditions such as diabetes and obesity. Currently, these rates are estimated using methods that do not account for the full complexity of intracellular biochemical reaction networks, and therefore often lead to inconsistent results. In this study, we are conducting metabolic flux analysis (MFA) studies using a unique formulation of 13C- and 2H-labeled glucose tracers and Gas Chromatography-Mass Spectrometry (GC-MS) profiling in order to understand the regulation of liver glucose fluxes in both fasted and fed Sprague-Dolly rats. By analyzing GC-MS labeling data of plasma glucose and lactate using our custom MFA software tools, we are developing novel strategies to quantify whole-body glucose metabolism using an integrated experimental and computational approach.