Research Areas: Animal Physiology, Cell Biology, Ion Channels, Heart Disease, Diabetes
The major focus of our research is to examine the basis of heart disease and diabetes. More specifically, my laboratory investigates the biophysical properties and cellular regulation of cardiac and pancreatic ion channels, explores the role of SNARE proteins in the heart and pancreatic islets, investigates the effects of cholesterol of islet cell function, and examines the mechanism associated with myocardial ischemic preconditioning protection.
Role of Cellular Cholesterol in Islet Stimulus-Secretion Coupling
Pancreatic islet alpha- and beta-cells play an important role in regulating glycemic homeostasis. We have shown the regulation of beta-cell voltage-gated Ca2+ channels and voltage-gated K+ channels channels by SNARE (soluble N-ethylmaleimide sensitive factor attachment protein (SNAP) receptor) proteins. The direct physical and functional coupling of these channels with SNARE proteins suggests a close association of ion channels with insulin secretory vesicles. Our lab has shown beta-cell ion channels and SNARE proteins target to specialized cholesterol-rich lipid raft domains on the membranes. Modulating cholesterol levels in alpha- and beta-cells has profound effects on ion channel function and hormone secretion.
Beaudry JL , D'Souza A , Teich T , Tsushima R , Riddell MC. (2013). Exogenous glucocorticoids and a high-fat diet cause severe hyperglycemia and hyperinsulinemia and limit islet glucose responsiveness in young male Sprague-Dawley rats. Endocrinology 154(9): 3197-3208.
Dionyssiou MG, Nowacki NB, Hashemi S, Zhao J, Kerr A*, Tsushima RG, McDermott JC. (2013). Cross-talk between glycogen synthase kinase 3β (GSK3β) and p38MAPK regulates myocyte enhancer factor 2 (MEF2) activity in skeletal and cardiac muscle. Journal of Molecular and Cellular Cardiology 54:35-44.
Tsushima RG. (2011). Second-phase insulin secretion gets cool.American journal of physiology. Endocrinology and Metabolism 301(6): E1070-E1071.
Gonzalez R, Perry RL, Gao X*, Gaidhu MP, Tsushima RG, Ceddia RB, Unniappan S. (2011). Nutrient responsive nesfatin-1 regulates energy balance and induces glucose-stimulated insulin secretion in rats. Endocrinology 152(10): 3628-3637.
Chao CC, Mihic A*, Tsushima RG, Gaisano HY. (2011). SNARE protein regulation of cardiac potassium channels and atrial natriuretic factor secretion. Journal of Molecular and Cellular Cardiology. 50(3): 401-407.
Gonzalez R, Reingold BK*, Gao X*, Gaidhu MP, Tsushima RG, Unniappan S. (2011). Nesfatin-1 exerts a direct, glucose-dependent insulinotropic action on mouse islet β- and MIN6 cells.The Journal of Endocrinology 208(3): R9-R16.
Kang Y, Zhang Y , Liang T , Leung YM , Ng B , Xie H , Chang N , Chan J , Shyng SL , Tsushima RG, Gaisano HY. (2011). ATP modulates interaction of syntaxin-1A with sulfonylurea receptor 1 to regulate pancreatic beta-cell KATP channels.The Journal of Biological Chemistry 286(7): 5876-5883.