Adults with diabetes have a 2-4 fold risk of heart disease and stroke, which are the number one cause of death for over 65% of people with diabetes.1 Almost 40% of people with type 2 diabetes are obese which is itself a major risk factor for cardiovascular disease.2 Understanding the pathology of insulin resistance will lead to novel therapies for the treatment of diabetes, and successful treatment of diabetes will decrease cardiovascular disease. Metabolic dysfunction such as decreased glucose uptake and increased lipolysis is a hallmark of defective insulin signaling in adipose tissue but can also result from defective extracellular nucleotide signaling. An important question is what controls extracellular nucleotide signaling in adipose tissue. We hypothesize that Pannexin 1 (Panx1) channels fulfill this role. We have convincing preliminary data which establishes for the first time that Panx1 is expressed and functional on adipocytes. We show that adipocytes which lack Panx1 do not increase glucose uptake in response to insulin. We have generated an adipocyte-specific Panx1 KO mouse (adipPanx1 KO) to study the role of Panx1 in adipose tissue. We hypothesize that Panx1 is a critical regulator of glucose and lipid homeostasis in adipocytes through the control of extracellular nucleotide signaling and that adipocyte-specific Panx1 KO mice will become more insulin resistant in a model of diet-induce obesity.
|Program type||Predoctoral Fellowship|
|Effective start/end date||07/01/2014 → 08/12/2015|