Adipocytes, skeletal myocytes and some neurons express a specific isoform of the glucose transporter protein, Glut4. Under basal conditions this transporter is localized in intracellular membrane vesicles which fuse with the plasma membrane upon insulin administration. Translocation of Glut4 plays a major role in post-prandial glucose clearance and, more generally, in glucose sensing and metabolic homeostasis in the body. For a number of years, my lab has been involved in the dissection of the “Glut4 pathway” in various insulin-sensitive cells.
Another key physiological function of insulin is to inhibit lipolysis and to promote storage of triglycerides in fat tissue. We have discovered two novel pathways of regulation of lipolysis by insulin. One of these pathways is mediated by the insulin- and nutrient-sensitive mammalian Target of Rapamycin Complex 1, while the other is mediated by the transcription factor FoxO1. Currently, we are engaged in the dissection of both pathways at the molecular level.
Fat represents an important secretory tissue in the body. Unlike typical endocrine and exocrine cells, adipocytes produce and secret several physiologically important proteins, such as leptin, adiponectin, lipoprotein lipase, etc. and switch the secretory process from one protein to another in response to changing metabolic conditions. We are exploring connections between food intake, obesity and secretion of adipokines in order to understand the central role of fat tissue in the orchestrating the overall response of the organism to changing metabolic conditions.