The Charron Laboratory works on two classes of proteins that play critical roles in regulation of glucose homeostasis and energy balance. Specifically, we study role of the glucose transporters GLUT4 and GLUT8 and also the glucagon receptor (Gcgr) in glucose homeostasis and insulin sensitivity. Using transgenic and targeted gene strategies, we have generated mouse models to define the role of these proteins in cellular and whole body metabolism and energy balance. The incidence of diabetes and obesity has reached epidemic proportions and treatment and diagnostic strategies are inadequate. The complications of diseases of insulin resistance are vast and include heart attack and stroke. In addition to genetic factors, the incidence of diabetes and obesity are influenced by environmental factors such as diet and exercise. Strong evidence derived from experimental animal models and human epidemiology suggests that perturbation of the early developmental environment (e.g. nutrient, stress, toxins) has lasting effects that enhance the offspring’s susceptibility to metabolic and other diseases. It is thought that these effects are mediated through alterations in the epigenome. Alterations in DNA methylation are measured as they represent the most stable epigenomic modifications. Mouse models are being used to evaluate the influence of maternal diet and metabolic status on the fetal/neonatal epigenome. The stability of these epigenetic signatures and their association with disease incidence are under investigation. A prospective clinical study has begun to evaluate the impact of a common environmental toxicant on DNA methylation profiles in umbilical cord and peripheral blood T cells and subsequent development of childhood obesity. We hope to identify an epigenetic signature of increased risk for obesity that may be used for early diagnosis and intervention. The ultimate goal of our studies is to define the molecular mechanism(s) underlying the pathogenesis of diabetes and obesity that may lead to novel therapeutics and potential cures for these and related metabolic diseases.
