Brain and Cognitive Science, Medicine, Pharmaceutical Sciences
Our lab studies the function of the brain in glucose homeostasis using mouse models. Obesity and insulin resistance are major risk factors for diabetes. However, obese and insulin resistant proopiomelanocortin (POMC)- and melanocortin 4 receptor (MC4R)-deficient mice and humans do not develop diabetes. To explain this paradox, we have demonstrated that POMC-deficient mice have elevated glycosuria (excretion of glucose in urine) because of decreased levels of renal glucose transporter GLUT2. We have further showed that the phenotype is due to suppressed sympathetic nervous system (SNS) activity. Our study led to the novel discovery of ArcPOMC/SNS/GLUT2 axis, which was published and highlighted in the March 2016 issue of Diabetes journal. Moreover, a follow up study with detailed molecular mechanism was published in Molecular Metabolism 2017. Mechanisms underlying POMC regulation of renal glucose reabsorption remain unclear. Our preliminary data indicate that hypothalamic MC4R is responsible for POMC peptides mediated effects on glucose transport. Therefore, during the summer research program, the scholar will further unravel the function of MC4R in glucose reabsorption. The scholar will utilize paraventricular nucleus-specific Mc4r knockout mouse model to delineate the function of the hypothalamic MC4R in glucose transport via the sympathetic nervous system. Moreover, the scholar will study the impact of epinephrine treatment on glucose transport in primary mouse hepatocytes and renal proximal tubule epithelial cells. All these experiments/methods are directly related to our main project involving the determination of the role of hypothalamic MC4R signaling in glucose transport/homeostasis.
Overall, our lab uses mouse models and state-of-the-art techniques associated with diabetes/obesity research and general molecular biology to understand the role of brain MC4R in glucose homeostasis.
Lab website: https://www.urmc.rochester.edu/labs/chhabra.aspx
Research area: Diabetes and Obesity