Molecular Coupling of Fuel Metabolism to Cell Function
Research in the Corkey laboratory is centered on the influence of the nutrient environment on metabolic regulation, ionic fluxes and signal transduction in with a particular focus on adipocytes, hepatocytes, fibroblasts and white cells from type 1 diabetic subjects and insulin secreting cells.
The main questions in the Corkey laboratory concern how fuels regulate secretion and the influence of glucose and fat on signal transduction. We seek to answer these questions by studying the signaling consequences of cellular energy state, the influence of fatty acids on protein kinases, the role of fatty acids and long chain fatty acyl CoA on signal transduction, and how fuel-induced signals control lipid partitioning, modulate secretion, electrical activity, metabolism and gene expression. Recent discoveries include an important role for redox and reactive oxygen species in insulin secretion and inhibition of the respiratory chain. The main tools used in the laboratory include single cell imaging of intracellular signals such as redox, ROS, Ca2+ and H+, plasma and mitochondrial membrane potential, and oxygen consumption. A new focus is on the effect of environmental agents on redox state and ROS generation and consequences for function. Animal models being used for these investigations include the Zucker lean, fatty and fatty diabetic rat models, several knock-out and transgenic mouse models and diet-induced obese rats and mice. Work is done in collaboration with scientists at Boston University, the Karolinska Institute, the Universities of Montreal, and Chicago.
1. Guo, W., Li, Y., Liang, W., Wong, S., and Corkey, B. E. (2012) Beta-mecaptoethanol Suppresses Inflammation and Induces Adipogenic Differentiation in 3T3-F442A Murine Preadipocytes, PLoSOne. 2012;7(7):e40958. PMCID: PMC3402440
2. Husni, NR, Jones, IV, AR, Simmons, A and Corkey, B. E. (2014) Fibroblasts From Type 1 Diabetics Exhibit Enhanced Ca2+ Mobilization after TNF or Fat Exposure. PLoS One. 2014; 9(1): e87068.. doi: 10.1371/journal.pone.0087068 PMCID: PMC3900712
3. Wikstrom, J., Mahdaviani, K., Sereda, S, Si, Y., Liesa, M., Las, G., Twig, G., Corkey, B., Cannon, B., Nedergaard, J. and Shirihai, O. (2014) Mitochondrial fragmentation is utilized by brown adipocytes as an amplification pathway for energy expenditure. EMBO J. 2014 Mar 3;33(5):418-36. doi: 10.1002/embj.201385014. Epub 2014 Jan 15. PMID:24431221. Free PMC Article
4. Corkey, B. E. (2012) Banting lecture 2011 Hyperinsulinemia: Cause or Consequence? Diabetes. 61:4-13 PMID:22187369.
5. Corkey, B. E. and Shirihai, O. (2012) Metabolic Master Regulators: Sharing Information among Multiple Systems, Trends Endocrinol Metab. 2012; 23(12): 594–601. PMCID: PMC3502692
6. Corkey, B. E. (2012) Diabetes: Have We Got It All Wrong? Insulin hypersecretion and food additives: cause of obesity and diabetes? Diabetes Care. 2012 Dec;35(12):2432-7. PMCID: PMC3507569