Touchstone Diabetes Center

Our goal in the Touchstone Diabetes Center is to study the cells and tissues that are affected by diabetes or its co-morbidities to improve diagnosis, treatment, and prevention of the major types of diabetes. Highly integrated efforts of several research groups contribute towards a multipronged approach aimed towards a better understanding of the cellular and systemic physiological responses to metabolic dysregulation. We work very closely with our colleagues in the Division of Hypothalamic Research, the Center for Human Nutrition and the Simmons Cancer Center.  The goal is to elucidate the key molecular pathways that lead to the development of Type I and Type II diabetes.  The strength of the Center relies on the ability to study these pathways at the cellular level, to translate these findings into genetic models in rodents and the ability to rapidly implement the results into clinical trials.

In the area of Type I diabetes, we are working on several preclinical models of b cell destruction.  In this type of diabetes, b cells in the pancreas -- which usually produce insulin -- are destroyed by the body’s own defense system.  We have developed valuable models of this disease.  Some of these models allow us to closely monitor the regeneration process, during which we can interfere pharmacologically as well as genetically to optimize conditions for maximal b cell recovery. Another critical cell type in islets, the a cell, is an important contributor towards hyperglycemia in the diabetic state due to unopposed secretion of glucagon in the absence of insulin. We want to better understand the role of glucagon in the diabetic state and determine whether there is room for a pharmacological intervention of glucagon signaling. Behavioral strategies to improve glycemic control in adolescent patients with Type 1 diabetes is also an area of local strength 

In the area of Type II diabetes, our main focus is on adipose tissue and its precursor cells. Type II diabetes is a metabolic disorder characterized by insulin resistance, relative insulin deficiency, hyperglycemia, dyslipidemia and is often associated with obesity.  Because of these factors, adipocyte physiology and the study of adipocyte-derived hormones and their impact on systemic insulin sensitivity comprise a key theme in our research efforts. Why does an increase in fat mass lead to increased risks for the development of diabetes, cardiovascular disease and cancer? How does the sexually dimorphic fat distribution (“male pattern” obesity vs. “female pattern” obesity) relate to differential susceptibility to disease? What constitutes a healthy fat pad? What are the critical lipids that mediate insulin resistance and inflammation? In this context, we focus on sphingolipids which include ceramide and sphingosine derivatives and explore their role in metabolic homeostasis. In this context, we also study non-adipocyte cells within adipose tissue and their relationship to insulin resistance and systemic inflammation in both rodent and human models.