We use stable isotope based metabolic flux analysis and metabolomics to derive functional information at the level of the metabolome. Functional information transmitted through the -omics cascade is inherent in the several shared metabolic networks. Metabolic flux analysis helps us to identify patterns of alterations pivotal to the development and progression of diseases like insulin resistance and diabetes. As an example, using the functional flux information derived form isotopomer analysis of plasma ketones (Figure) we profiled the progressive adaptation of hepatic ketogenesis during insulin resistance. This helped us to identify that mitochondrial fat oxidation is stimulated rather than impaired during initiation of insulin resistance.
Significant cross talk exists between nutrients, hormones and their molecular mediators to maintain energy homeostasis during health and disease. Defects in insulin signaling associated with insulin resistance and diabetes results in multiple metabolic derangements, either through altered nutrient transport or defective intracellular nutrient/molecular signaling mechanisms. These derangements are not limited to pathways of glucose and lipid metabolism, but also extend to pathways of urea and amino acid metabolism. My research interest is in identifying the shared metabolic defects contributing to the progression of insulin resistance and diabetes, especially in the liver. We use stable isotope based Mass Spectrometry and Nuclear Magnetic Resonance in combination with standard tools in molecular biology to profile glucose and mitochondrial metabolism. We study diet-induced/ genetically modified rodent models of disease under various metabolic perturbations including euglycemic hyperinsulinemic clamp and lipid challenge to tease out the metabolic alterations contributing to disease progression. My goal is to combine the functional metabolic flux information together with the several mechanisms of molecular regulation to understand the metabolic physiology during disease.
|Profiling intermediary metabolism by stable isotopes||Hepatic metabolism in insulin resistance and diabetes|
|Metabolomics by mass spectrometry|