Amira Klip, PhD, Hospital For Sick Children

Amira Klip, PhD
Amira Klip, PhD

Dr. Klip's laboratory has been studying the regulation of glucose uptake by insulin and muscle contraction, using an array of rat and mouse stable muscle cell lines that they have generated. These cells are platforms to study the intracellular traffic of vesicles containing GLUT4 glucose transporters (10,12,15,16,18). Current work focuses on how a series of signal transduction pathways activated by insulin or contraction-related stimuli impinge on intracellular stores of GLUT4 to make GLUT4 vesicles move to and fuse with the plasma membrane or to internalize from the cell surface (2,10,12). This requires participation of the IRS proteins, PI-3-kinase (15), Rac1 (5), Akt (17), AMPK (2,12,14), CaMKII (2), novel PKCs (2,13,14), Rab-GAP proteins (13,14), Rab GTPases (9), myosin motors (3,7), the actin cytoskeleton (3,7,13) and SNARES (4) for faithful congregation of signals that regulate GLUT4 vesicle traffic. How muscle cells are affected by inflammatory and insulin resistance-inducing environments are other aspects of their studies (1,6,8,11).

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References

  1. Pillon NJ, Li YE, Fink LN, Brozinick JT, Nikolayev A, Kuo MS, Bilan PJ, KlipA. (2014) Nucleotides released from palmitate-challenged muscle cells through pannexin-3 attract monocytes. Diabetes. 63: 3815-26.
  2. Li Q, Zhu X, Ishikura S, Zhang D, Gao J, Sun Y, Contreras-Ferrat A, Foley KP, Lavandero S, Yao Z, Bilan PJ, Klip A, Niu W. (2014) Ca²⁺ signals promote GLUT4 exocytosis and reduce its endocytosis in muscle cells. Am J Physiol Endocrinol Metab. Jul 15;307(2):E209-24.
  3. Sun Y, Chiu TT, Foley KP, Bilan PJ, Klip A. (2014) Myosin Va mediates Rab8A-regulated GLUT4 vesicle exocytosis in insulin-stimulated muscle cells. Mol Biol Cell. 25: 1159-70.
  4. Foley KP, Klip A. (2014) Dynamic GLUT4 sorting through a syntaxin-6 compartment in muscle cells is derailed by insulin resistance-causing ceramide. Biol Open. 3: 314-25.
  5. Chiu TT, Sun Y, Koshkina A, Klip A. (2013) Rac-1 superactivation triggers insulin-independent glucose transporter 4 (GLUT4) translocation that bypasses signaling defects exerted by c-Jun N-terminal kinase (JNK)- and ceramide-induced insulin resistance. J Biol Chem. 288:17520-31.
  6. Pillon NJ, Arane K, Bilan PJ, Chiu TT, Klip A. (2012) Muscle cells challenged with saturated fatty acids mount an autonomous inflammatory response that activates macrophages. Cell Commun Signal. 10: 30.
  7. Boguslavsky S, Chiu T, Foley KP, Osorio-Fuentealba C, Antonescu CN, Bayer KU, Bilan PJ, Klip A. (2012) Myo1c binding to submembrane actin mediates insulin-induced tethering of GLUT4 vesicles. Mol Biol Cell. 23: 4065-78.
  8. Kewalramani G, Fink LN, Asadi F, Klip A. (2011) Palmitate-activated macrophages confer insulin resistance to muscle cells by a mechanism involving protein kinase C θ and ε. PLoS One. 6: e26947.
  9. Sun Y, Bilan PJ, Liu Z, Klip A. (2010) Rab8A and Rab13 are activated by insulin and regulate GLUT4 translocation in muscle cells. Proc Natl Acad Sci U S A. 107: 19909-14.
  10. Ishikura S, Antonescu CN, Klip A. (2010) Documenting GLUT4 Exocytosis and Endocytosis in Muscle Cell Monolayers. Curr. Protoc. Cell Biol., John Wiley & Sons, Inc., 46: Unit 15.15: 1-9.
  11. Samokhvalov V, Bilan PJ, Schertzer JD, Antonescu CN, Klip A. (2009) Palmitate- and lipopolysaccharide-activated macrophages evoke contrasting insulin responses in muscle cells. Am J Physiol Endocrinol Metab. 296: E37-46.
  12. Antonescu CN, Díaz M, Femia G, Planas JV, Klip A. (2008) Clathrin-dependent and independent endocytosis of glucose transporter 4 (GLUT4) in myoblasts: regulation by mitochondrial uncoupling. Traffic. 9: 1173-90.
  13. Thong FS, Bilan PJ, Klip A. (2007) The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic. Diabetes. 56: 414-23.
  14. Wijesekara N, Tung A, Thong F, Klip A. (2006) Muscle cell depolarization induces again in surface GLUT4 via reduced endocytosis independently of AMPK. Am J Physiol Endocrinol Metab. 290: E1276-86.
  15. Ishiki M, Randhawa VK, Poon V, Jebailey L, Klip A. (2005) Insulin regulates the membrane arrival, fusion, and C-terminal unmasking of glucose transporter-4 via distinct phosphoinositides. J Biol Chem. 280: 28792-802.
  16. Rudich A, Konrad D, Török D, Ben-Romano R, Huang C, Niu W, Garg RR, Wijesekara N, Germinario RJ, Bilan PJ, Klip A. (2003) Indinavir uncovers different contributions of GLUT4 and GLUT1 towards glucose uptake in muscle and fat cells and tissues. Diabetologia 46: 649-58.
  17. Wang Q, Somwar R, Bilan PJ, Liu Z, Jin J, Woodgett JR, Klip A. (1999) Protein kinase B/Akt participates in GLUT4 translocation by insulin in L6 myoblasts. Mol Cell Biol. 19: 4008-18.
  18. Wang Q, Khayat Z, Kishi K, Ebina Y, Klip A. (1998) GLUT4 translocation by insulin in intact muscle cells: detection by a fast and quantitative assay. FEBS Letters 427: 193-7.