Division of Endocrinology Dept of Medicine

My lab employs a systems biology framework for metabolic profiling, to investigate molecular mechanisms underlying the metabolic network impacted by insulin action. Our approach is unique in the use of stable isotope-based metabolic flux phenotyping, utilizing gas chromatography/mass spectrometry (GC/MS), to find the locus of metabolic dysregulation in a particular tissue, or in substrate exchange between tissues. The use of GC/MS to guide our integrated physiology investigations is how we differ from those in the field who primarily use large scale transcriptosomic and proteomic analyses in an attempt to find a metabolic locus. LC/MS/MS is also used to do metabolite profiling, in order to correlate the rate of substrate exchange (flux) with the concentration of metabolites in a given tissue. Specifically, my lab pursues in vitro and in vivo flux/metabolite profiling investigations to validate the hypothesis that insulin signaling cannot be separated from the metabolic response, such as glucose and fatty acid metabolism. Our in vitro studies focus mainly on hepatic cell lines and primary hepatocyte culture. Our in vivo studies range from targeted mouse knockouts of orphan nuclear receptor action, to specific mouse knockouts of selected signaling effectors in the insulin/PI3-K pathway. We are beginning human studies involving stable isotopes and GC/MS, to see if we can easily determine the extent of peripheral versus hepatic insulin resistance.

(631) 444-9464, Irwin.kurland@stonybrook.edu