Konstantin V. Kandror
Lab Phone: 617-638-5068
BS, MS, Moscow State University, Moscow, Russia
PhD, Bakh Institute of Biochemistry, Moscow, Russia
Senior Research Scientist
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.
- Fat specific protein 27 inhibits lipolysis by facilitating the inhibitory effect of Egr1 on transcription of adipose triglyceride lipase. Singh M, Kaur R, Lee MJ, Pickering RT, Sharma VM, Puri V, Kandror KV. J Biol Chem. 2014 Apr 17. [Epub ahead of print]
- 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.
- 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.
- The first luminal loop confers insulin responsiveness to glucose transporter 4. Kim JY, Kandror KV. Mol Biol Cell. 2012 Mar;23(5):910-7.
- The multi-level action of fatty acids on adiponectin production by fat cells. Karki S, Chakrabarti P, Huang G, Wang H, Farmer SR, Kandror KV. PLoS One. 2011;6(11):e28146.
- Adipose triglyceride lipase: a new target in the regulation of lipolysis by insulin. Chakrabarti P, Kandror KV. Curr Diabetes Rev. 2011 Jul;7(4):270-7. Review.
- SIRT1 controls lipolysis in adipocytes via FOXO1-mediated expression of ATGL. Chakrabarti P, English T, Karki S, Qiang L, Tao R, Kim J, Luo Z, Farmer SR, Kandror KV. J Lipid Res. 2011 Sep;52(9):1693-701.
- The sugar is sIRVed: sorting Glut4 and its fellow travelers. Kandror KV, Pilch PF. Traffic. 2011 Jun;12(6):665-71.
- Biogenesis and regulation of insulin-responsive vesicles containing GLUT4. Bogan JS, Kandror KV. Curr Opin Cell Biol. 2010 Aug;22(4):506-12.
- Mammalian target of rapamycin complex 1 suppresses lipolysis, stimulates lipogenesis, and promotes fat storage. Chakrabarti P, English T, Shi J, Smas CM, Kandror KV. Diabetes. 2010 Apr;59(4):775-81.
- Proteomic analysis of GLUT4 storage vesicles reveals LRP1 to be an important vesicle component and target of insulin signaling. Jedrychowski MP, Gartner CA, Gygi SP, Zhou L, Herz J, Kandror KV, Pilch PF. J Biol Chem. 2010 Jan 1;285(1):104-14.
- Cerebellar neurons possess a vesicular compartment structurally and functionally similar to Glut4-storage vesicles from peripheral insulin-sensitive tissues. Bakirtzi K, Belfort G, Lopez-Coviella I, Kuruppu D, Cao L, Abel ED, Brownell AL, Kandror KV. J Neurosci. 2009 Apr 22;29(16):5193-201.
- FoxO1 controls insulin-dependent adipose triglyceride lipase (ATGL) expression and lipolysis in adipocytes. Chakrabarti P, Kandror KV. J Biol Chem. 2009 May 15;284(20):13296-300.
- Mechanisms for increased myocardial fatty acid utilization following short-term high-fat feeding. Wright JJ, Kim J, Buchanan J, Boudina S, Sena S, Bakirtzi K, Ilkun O, Theobald HA, Cooksey RC, Kandror KV, Abel ED. Cardiovasc Res. 2009 May 1;82(2):351-60.
- The C-terminus of GLUT4 targets the transporter to the perinuclear compartment but not to the insulin-responsive vesicles. Li LV, Bakirtzi K, Watson RT, Pessin JE, Kandror KV. Biochem J. 2009 Apr 1;419(1):105-12
- Self-assembly of Glut4 storage vesicles during differentiation of 3T3-L1 adipocytes. Shi J, Huang G, Kandror KV. J Biol Chem. 2008 Oct 31;283(44):30311-21.
- The mammalian target of rapamycin complex 1 regulates leptin biosynthesis in adipocytes at the level of translation: the role of the 5′-untranslated region in the expression of leptin messenger ribonucleic acid. Chakrabarti P, Anno T, Manning BD, Luo Z, Kandror KV. Mol Endocrinol. 2008 Oct;22(10):2260-7.
- Study of glucose uptake in adipose cells. Shi J, Kandror KV. Methods Mol Biol. 2008;456:307-15.
- An ACAP1-containing clathrin coat complex for endocytic recycling. Li J, Peters PJ, Bai M, Dai J, Bos E, Kirchhausen T, Kandror KV, Hsu VW. J Cell Biol. 2007 Jul 30;178(3):453-64.
- The luminal Vps10p domain of sortilin plays the predominant role in targeting to insulin-responsive Glut4-containing vesicles. Shi J, Kandror KV. J Biol Chem. 2007 Mar 23;282(12):9008-16.