Konstantin V. Kandror
Boston University School of Medicine
Silvio Conte Building, K120D
72 E. Concord Street
Boston, MA 02118
Lab Phone: 617-638-5308, 617-638-5068
BS, MS, Moscow State University, Moscow, Russia
PhD, Bakh Institute of Biochemistry, Moscow, Russia
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. Recently, 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 transcriptional 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.
- Insulin responsiveness of glucose transporter 4 in 3T3-L1 cells depends on the presence of sortilin. Huang G, Buckler-Pena D, Nauta T, Singh M, Asmar A, Shi J, Kim JY, Kandror KV. Mol Biol Cell. 2013 Oct;24(19):3115-22. doi: 10.1091/mbc.E12-10-0765. Epub 2013 Aug 21.
- Insulin Inhibits Lipolysis in Adipocytes via the Evolutionarily Conserved mTORC1-Egr1-ATGL-Mediated Pathway. Chakrabarti P, Kim JY, Singh M, Shin YK, Kim J, Kumbrink J, Wu Y, Lee MJ, Kirsch KH, Fried SK, Kandror KV. Mol Cell Biol. 2013 Sep;33(18):3659-66. doi: 10.1128/MCB.01584-12. Epub 2013 Jul 15.
- Kim, J-Y. & Kandror, K.V. The first luminal loop confers insulin responsiveness to the glucose transporter 4. Mol.Biol. Cell, 2012, v. 23, #5, 910-917.
- Karki, S., Chakrabarti, P., Huang, G., Wang, H., Farmer, S.R., and Kandror, K.V. The multi-level action of fatty acids on adiponectin production by fat cells, Plos One, 2011, v.6, #11, e28146.
- Chakrabarti, P., and Kandror, K.V. Adipose triglyceride lipase: a new target in regulation of lipolysis by insulin. Current Diabetes Reviews, 2011, 7, 270-277.
- Kandror KV, Pilch PF. The sugar is sIRVed; sorting Glut4 and its fellow travelers. Traffic, 2011, 12, #6, 665-71.
- Chakrabarti P., English T., Karki S., Qiang L., Tao R., Kim J., Luo Z., Farmer S., and Kandror, K.V. SIRT1 controls lipolysis in adipocytes via FoxO1-mediated expression of ATGL, J.Lipid Res., 2011, 52, 1693-1701.
- Bogan JS, Kandror KV. Biogenesis and regulation of insulin-responsive vesicles containing GLUT4. Curr. Opin. Cell Biol. 2010, 22, 506-512.
- Chakrabarti, P., English, T., Shi, J., Smas, C. and Kandror, K.V. The mTOR complex 1 suppresses lipolysis, stimulates lipogenesis and promotes fat storage, Diabetes, 2010, 59, #4, 775-781.
- Jedrychowski, M.P., Gygi, S.P., Gartner, C.A., Herz, J., Kandror, K.V. and Pilch, P.F. Proteomic analysis of Glut4 Storage Vesicles (GSVs) reveals LRP1 to be an important vesicle component and target of insulin signaling, J.Biol.Chem., 2010, v. 285, #1, 104-14.
- Chakrabarti, P., and Kandror, K.V. FoxO1 controls insulin-dependent ATGL expression and lipolysis in adipocytes. J.Biol.Chem., 2009, v. 284, #20, 13296-13300.
- Bakirtzi, K., Belfort, G., Lopez-Coviella, I., Kuruppu, D., Cao, L., Abel, E.D., Brownell, A.-D., and Kandror, K.V. Cerebellar neurons possess a vesicular compartment structurally and functionally similar to Glut4-storage vesicles from peripheral insulin-sensitive tissues. J. Neurosci., 2009, v. 29, #16, 5193-5201.
- Wright, J.J., Kim, J., Buchanan, J., Bakirtzi, K., Sena, S., Ilkun, O., Theobald, H.A., Cooksey, R.C., Boudina, S., Kandror, K.V. and Abel, E.D. Mechanisms for increased myocardial fatty acid utilization following short-term high fat feeding. Cardiovascular Research, 2009, v.82, #2, 351-360.
- Li, L.V., Bakirtzi, K., Watson, R., Pessin, J.E., and Kandror, K.V. The C-terminus of Glut4 targets the transporter to the perinuclear compartment but not to the insulin-responsive vesicles. Biochem. J., 2009, v.419, #1, 105-112.
- Chakrabarti, P., Anno, T., Manning B.D., Luo, Z., and Kandror, K.V. The mTOR complex 1 regulates leptin biosynthesis in adipocytes at the level of translation. The role of the 5’-UTR in the expression of leptin mRNA. Mol.Endocrinology, 2008, v. 22, #10, 2260-2267.
- Shi, J., Huang, G., and Kandror, K.V. Self-assembly of Glut4-storage vesicles in differentiating 3T3-L1 adipocytes. J.Biol.Chem., 2008, v. 283, #44, 30311-30321.
- Li, J., Peters, P.J., Dai, J., Bai, M., Bos, E., Kirchhausen, T., Kandror, K.V., and Hsu, V.W. An ACAP1-containing clathrin coat complex for endocytic recycling, J. Cell Biol., 2007, v.178, #3, 453-464.
- Shi, J. and Kandror K.V. The luminal Vps10p domain of sortilin plays the predominant role in targeting to insulin-responsive Glut4-containing vesicles”, J.Biol.Chem., 2007, v.282, #12, 9008-9016.