Our research program seeks to understand the effect of various factors on the regulation of gluconeogenesis. Static measurements of metabolites typically lack the details necessary to identify the differences in the metabolic pathways between a clinical and healthy condition. Turnover of metabolic pathways can be measured by stable isotope tracer infusions. Such measurements provide definite evidence for a metabolic dysfunction when measured in a disease condition in contrast to a healthy state. My laboratory in collaboration with other clinicians/investigators carry out total glucose production and gluconeogenesis rates measurements in human volunteers and in genetic mice models using stable isotope labeled glucose and water (natural and non-radioactive). We measure isotopic enrichments in plasma, tissue, and urine samples after the infusion of stable isotope tracers using highly sophisticated mass spectrometry-based techniques. We have developed and published a simple and reproducible method to measure absolute rates of total gluconeogenesis that includes contribution from all substrates using deuterium labeled water, which can be applied in preterm infants and small lab animals utilizing small plasma sample. With this method, we have measured rates of gluconeogenesis in preterm infants and in post-surgical children using 25 μl of blood and demonstrated that glucose production was not fully suppressed during hyperglycemia because of continued production of glucose from GNG. This methodology also enables the indirect estimation of glycogenolysis and provides the possibility to study the effect of hormones or small molecules on gluconeogenic pathway.
Total Energy Expenditure
Our research program also studies the effect of diets, diseases, and clinical treatments on total energy expenditure, total body water, and body composition. Energy is required for muscular activity, growth, reproduction, and synthesis of metabolites such as proteins, fatty acids, nucleic acids, and steroids, which are essential to maintain basal metabolic functions as well as optimal growth and development. We use the stable isotopes of hydrogen and oxygen (natural and nonradioactive) to achieve these measurements. The doubly labeled water method provides an average energy expenditure for a period of 5-14 d depending on the age of the study population. The procedure is noninvasive, nonrestrictive, and reflective of actual energy expenditure under free-living conditions. Currently the doubly labeled water method is considered to be the reference method for the estimation of energy expenditure or caloric requirements in free-living subject.