|Guim Kwon, Ph.D.
Associate Professor of Pharmaceutical Sciences
Fax: (618) 650‑5145
B.S., 1986, University of Michigan
Ph.D., 1992, University of Michigan
Postdoctoral, 1992-1997, Washington University School of Medicine in St. Louis
Research Instructor, 1998-2005, Washington University School of Medicine in St. Louis
My research interests focus on providing strategies for therapeutic intervention for both type 1 and type 2 diabetes mellitus. I have three on-going projects including 1) understanding the link between obesity and type 2 diabetes, 2) designing and validating an implantation model for ß-cell replacement therapy, and 3) developing control algorithms for a closed-loop artificial pancreas described below.
1. The link between obesity and type 2 diabetes
Type 2 diabetes mellitus (T2DM) is characterized by a progressive loss of insulin-secreting ß-cell function and mass associated with obesity. There is a fundamental gap in understanding how chronic nutrient overload alters ß-cell function. Elucidation of nutrient-induced changes in ß-cell physiology may provide insight that leads to the development of pharmaceutical approaches to preserve ß-cell function and mass in susceptible obese individuals. My research interests focus on elucidating the alterations in ß-cell metabolic signaling under chronic nutrient overload and their role in ß-cell defects using isolated rat and human islets as well as high fat diet-fed obese mice. The causal relationship between the adaptive responses and ß-cell defects are currently investigated by measuring insulin secretion, insulin content, and ß-cell apoptosis under the conditions of excess nutrients in the presence and absence of inhibitors that block lipid accumulation, ß-cell hypertrophy, and nitrative and oxidative stress (peroxynitrite generation). Our approaches are novel and innovative in that we have developed microscopic methodologies for the simultaneous assessment of multi-factorial ß-cell responses to metabolic perturbations in addition to traditional biochemical assays. Using fluorescent microscopy, we are able to quantitate lipid droplets, insulin content, and intra-islet cell size, and study alterations in islet architecture.
2. Designing and validating an implantation model for ß-cell replacement therapy
Type 1 diabetes mellitus (T1DM) is a chronic, progressive autoimmune disease caused by selective destruction of insulin-producing ß-cells within the pancreatic islets of Langerhans. Insulin delivered through an insulin pump or daily injections is essential to sustain life for these patients. Despite careful monitoring, a subset of patients with complicated T1DM are at high risk of life-threatening hypoglycemia episodes. Emerging new treatments for these patients include ß-cell replacement therapy and non-transplant technologies such as an artificial pancreas. Islet transplantation, when successful, eliminates hypoglycemic episodes, slows or prevents the progression of complications, and improves patient quality of life. However, major hurdles for this therapy include poor islet survival, side effects of life-long immunosuppressants and shortage of islets from donors. To circumvent islet shortage and post-transplantation rejection, islet encapsulation within semi-permeable, biocompatible membrane as a strategy to mask islets from host immune cells has emerged. However, there is still a gap to meet challenges of prolonging islet survival in large due to lack of adequate oxygen and nutrient supply. In collaboration with a faculty in the Biomedical Engineering at St. Louis University, we are developing an islet implantation model that promotes vascularization and, thus, improves islet survival, provides immune privilege and is readily retrievable and re-implantable while minimally invasive.
3. Developing algorithms for a closed-loop artificial pancreas
A closed-loop artificial pancreas is a technology under investigation to help controlling blood glucose levels automatically in type 1 diabetic patients, replacing the endocrine functionality of the pancreas. The artificial pancreas is composed of an insulin pump, a continuous glucose monitoring sensor (CGM), and a control algorithm that processes the input from the CGM, determines appropriate amounts of insulin, and commands the delivery of insulin through the insulin pump. We have successfully developed a streptozotocin-induced diabetic rat model with an open-loop artificial pancreas. In collaboration with faculties in Industrial Engineering at SIUE, we are currently working on developing control algorithms to advance it to a closed-loop artificial pancreas.
Rohatgi, N., Remedi, M. S., Kwon, G., Pappan, K. L., Marshall, C. A., and McDaniel, M. L. (2010) Therapeutic Strategies to Increase Human ß-Cell growth and proliferation by regulating mTOR and GSK-3/ß-Catenin pathways. The Open Endo. J. 4(2001), 40-54
Vernier, S., Chiu, A., Schober, J., Weber, T., Nguyen, P., Luer, M., McPherson, T., Wanda, P. E., Marshall, C. A., Rohatgi, N., McDaniel, M. L., Greenberg, A. S., Kwon, G. (2012) ß-cell metabolic alterations under chronic nutrient overload in rat and human islets. Islets 4 (6): 379-392
Johns, M., Fyalka, R., Shea, J. A., Neumann, W. L., Rausaria, S., Msengi, E. N., Imani-Nejad, M., Zollars, H., McPherson, T., Schober, J., Wooten, J., Kwon, G. (2015) SR-135, a peroxynitrite decomposing catalyst, enhances ß-cell function and survival in B6D2F1 mice fed a high fat diet. Arch Biochem Biophys 577-578: 49-59
Johns, M., Abadi, S. E. M., Malik, N., Lee, J. J., Neumann, W. L., Rausaria, S., Imani-Nejad, M., McPherson, T., Schober, J., Kwon, G. (2016) Oral Administration of SR-110, a Peroxynitrite Decomposing Catalyst, Enhances Glucose Homeostasis, Insulin Signaling, and Islet Architecture in B6D2F1 Mice Fed a High Fat Diet. Arch Biochem Biophys.