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Summary
Dr. Amira Klip is a senior scientist in the Cell Biology Program at SickKids Research Institute and Professor of Paediatrics, Biochemistry, and Physiology at the University of Toronto. In order to understand the process of insulin resistance, a problem for both type 1 and type 2 diabetes, Klip studies insulin action and the cellular and molecular steps involved in this process. She directs a laboratory of ten graduate students/postdoctoral fellows, one technician, and one research associate and works with several pharmaceutical companies to screen and identify modes of action of potential anti-diabetic drugs.
Klip received a PhD in Biochemistry (Mexico City, 1976), performed postdoctoral work in Toronto and Zurich, and joined The Hospital for Sick Children (SickKids) in 1979. She is a Canadian Institutes of Health Research Distinguished Scientist and a fellow of the Royal Society of Canada. She has been a member of the CIHR grant panels on cell physiology, cell biology, and mechanisms of disease. She is an executive member of the Banting and Best Diabetes Centre at the University of Toronto.
Klip’s research is currently funded by the Canadian Institutes of Health Research (CIHR) operating grants and the Canadian Diabetes Association (CDA) Grant-in-Aid.
| Current Institution | University of Toronto |
| Department | Biochemistry |
| Disciplines | |
| Address | Toronto British Columbia Canada Phone: 416-813-6392 |
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Education
Work Experience
Professor
University of Toronto
Achievements
General
Publication Summary
Publications
- Chiu TT, Patel N, Shaw AE, Bamburg JR, Klip A: (2010) Arp2/3- and cofilin-coordinated actin dynamics is required for insulin-mediated GLUT4 translocation to the surface of muscle cells. Mol. Biol. Cell, Epub ahead of print Sept 1.
- Contreras-Ferrat AE, Toro B, Bravo R, Parra V, Vásquez C, Ibarra C, Mears D, Chiong M, Jaimovich E, Klip A, Lavandero S: (2010) An inositol 1,4,5-triphosphate (IP3)-IP3 receptor pathway Is required for insulin-stimulated glucose transporter 4 translocation and glucose uptake in cardiomyocytes. Endocrinol., 151: 10: Epub ahead of print Aug 4.
- Niu W, Bilan PJ, Yu J, Gao J, Boguslavsky S, Schertzer JD, Chu G, Yao Z, Klip A: (2010) PKCe regulates contraction-stimulated GLUT4 traffic in skeletal muscle cells. J. Cell. Physiol., Epub ahead of print July 23.
- Schwenk RW, Dirkx E, Coumans WA, Bonen A, Klip A, Glatz JFC, Luiken JJFP: (2010) Requirement for distinct vesicle-associated membrane proteins in insulin- and AMP-activated protein kinase (AMPK)-induced translocation of GLUT4 and CD36 in cultured cardiomyocytes. Diabetologia, 53: 10: 2209-19.
- Niu W, Bilan PJ, Ishikura S, Schertzer JD, Contreras-Ferrat A, Fu Z, Liu J, Boguslavsky S, Foley KP, Liu Z, Li J, Chu G, Panakkezhum T, Lopaschuk GD, Lavandero S, Yao Z, Klip A: (2010) Contraction-related stimuli regulate GLUT4 traffic in C2C12-GLUT4myc skeletal muscle cells. Am. J. Physiol. Endocrinol. Metab., 298: E1058-71.
- Hartig SM, Ishikura S, Hicklen RS, Feng Y, Blanchard EG, Voelker KA, Pichot CS, Grange RW, Raphael RM, Klip A, Corey SJ: (2009) The F-BAR protein CIP4 promotes GLUT4 endocytosis through bidirectional interactions with N-WASp and Dynamin-2. J. Cell Sci., 122: 2283-91.
- Schertzer JD, Antonescu CN, Bilan PJ, Jain S, Huang X, Liu Z, Bonen A, Klip A: (2009) A transgenic mouse model to study glucose transporter 4myc regulation in skeletal muscle. Endocrinol., 150: 1935-40.
- Zaid H, Talior-Volodarsky I, Antonescu C, Liu Z, Klip A: (2009) GAPDH binds GLUT4 reciprocally to hexokinase-II and regulates glucose transport activity. Biochem. J., 419: 475-84.
- 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.
- Wood TE, Dalili S, Simpson CD, Hurren R, Mao X, Saiz FS, Gronda M, Eberhard Y, Minden MD, Bilan PJ, Klip A, Batey RA, Schimmer AD: (2008) A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death. Mol. Cancer Ther., 7: 3546-55.
- Ishikura S, Klip A: (2008) Muscle cells engage Rab8A and myosin Vb in insulin-dependent GLUT4 translocation. Am. J. Physiol. Cell Physiol., 295: C1016-25.
- Randhawa VK, Ishikura S, Talior-Volodarksy I, Cheng AW, Patel N, Hartwig JH, Klip A: (2008) GLUT4 vesicle recruitment and fusion are differentially regulated by Rac, AS160, and Rab8A in muscle cells. J. Biol. Chem., 283: 27208-19.
- Talior-Volodarsky I, Randhawa VK, Zaid H, Klip A: (2008) α-Actinin-4 is selectively required for insulin-induced GLUT4 translocation. J. Biol. Chem., 283: 25115-23.
- Antonescu CN, Díaz M, Femia G, Planas JV, and Klip A: (2008) Clathrin-dependent and independent endocytosis of glucose transporter 4 (GLUT4) in myoblasts: regulation by mitochondrial uncoupling. Traffic, 9: 1173-90.
- Dugani CB, Randhawa VR, Cheng AW, Patel N, and Klip A: (2008) Selective regulation of the perinuclear distribution of glucose transporter 4 (GLUT4) by insulin signals in muscle cells. Eur. J. Cell Biol., 87: 337-51.
- Roher N, Samokhvalov V, Díaz M, MacKenzie S, Klip A, and Planas JV: (2008) The proinflammatory cytokine tumor necrosis factor-a increases the amount of glucose transporter-4 at the surface of muscle cells independently of changes in interleukin-6. Endocrinol., 149: 1880-9.
- Ishikura S, Bilan PJ, and Klip A: (2007) Rabs 8A and 14 are targets of the insulin-regulated Rab-GAP AS160 regulating GLUT4 traffic in muscle cells. Biochem. Biophys. Res. Commun., 353: 1074-9.
- Thong FSL, Bilan PJ, and 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.
- JeBailey L, Wanono O, Niu W, Roessler J, Rudich A, and Klip A: (2007) Ceramide- and oxidant-Induced insulin resistance involve loss of insulin-dependent Rac-activation and actin remodeling in muscle cells. Diabetes, 56: 394-403.
- Wijesekara N, Tung A, Thong F, and Klip A: (2006) Muscle cell depolarization induces a gain in surface GLUT4 via reduced endocytosis independently of AMPK. Am. J. Physiol. Endocrinol. Metab., 290: E1276-86.
- Thirone ACP, JeBailey L, Bilan PJ, and Klip A: (2006) Opposite effect of JAK2 on insulin-dependent activation of mitogen-activated protein kinases and Akt in muscle cells: possible target to ameliorate insulin resistance. Diabetes, 55: 942-51.
- Foster LJ, Rudich A, Talior I, Patel N, Huang X, Furtado LM, Bilan PJ, Mann M, and Klip A: (2006) Insulin-dependent interactions of proteins with GLUT4 revealed through stable isotope labeling by amino acids in cell culture (SILAC). J. Proteome Res., 5: 64-75.
- Ishiki M, Randhawa VK, Poon V, JeBailey L, and 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.
- Antonescu CN, Huang C, Niu W, Liu Z, Eyers PA, Heidenreich KA, Bilan PJ, and Klip A: (2005) Reduction of insulin-stimulated glucose uptake in L6 myotubes by the protein kinase inhibitor SB203580 is independent of p38 MAPK activity. Endocrinol., 146: 3773-81.
- Huang C, Thirone ACP, Huang X, and Klip A: (2005) Differential contribution of insulin receptor substrates 1 versus 2 to insulin signaling and glucose uptake in L6 myotubes. J. Biol. Chem., 280: 19426-35.
- Konrad D, Rudich A, Bilan P J, Patel N, Richardson C, Witters LA, and Klip A: (2005) Troglitazone causes acute mitochondrial membrane depolarization and an AMPK-mediated increase in glucose phosphorylation in muscle cells. Diabetologia, 48: 954-66.
- Wijesekara N, Konrad D, Eweida M, Jefferies C, Liadis N, Giacca A, Crackower M, Suzuki A, Mak TW, Kahn CR, Klip A, and Woo M: (2005) Muscle-specific pten deletion protects against insulin resistance and diabetes. Mol. Cell. Biol., 25: 1135-45.
- Randhawa VK, Thong FSL, Lim DY, Li D, Garg RR, Rudge R, Galli T, Rudich A, and Klip A: (2004) Insulin and hypertonicity recruit GLUT4 to the plasma membrane of muscle cells by Using N-Ethylmaleimide-sensitive factor-dependent SNARE mechanisms but different v-SNAREs: role of TI-VAMP. Mol. Biol. Cell, 15: 5565-73.
- Török D, Patel N, JeBailey L, Thong FSL, Randhawa VK, Klip A, and Rudich A: (2004) Insulin but not PDGF rely on actin remodeling and on VAMP2 for GLUT4 translocation in myoblasts. J. Cell Sci., 117: 5447-55.
- Sweeney G, Garg RR, Ceddia RB, Li D, Ishiki M, Somwar R, Foster LJ, Neilsen PO, Prestwich GD, Rudich A, and Klip A: (2004) Intracellular delivery of phosphatidylinositol (3,4,5)-trisphosphate causes incorporation of glucose transporter 4 into the plasma membrane of muscle and fat cells without increasing glucose uptake. J. Biol. Chem., 279: 32233-42.
- JeBailey L, Rudich A, Huang X, Di Ciano-Oliveira C, Kapus A, and Klip A: (2004) Skeletal muscle cells and adipocytes differ in their reliance on TC10 and Rac for insulin-induced actin remodeling. Mol. Endocrinol., 18: 359-72.
- Patel N, Rudich A, Khayat Z, Garg R, and Klip A: (2003) Intracellular segregation of phosphatidylinositol-3,4,5-trisphosphate by insulin-dependent actin remodeling in L6 skeletal muscle cells. Mol. Cell. Biol., 23: 4611-26.
- Rudich A, Konrad D, Török D, Ben-Romano R, Huang C, Niu W, Garg RR, Wijesekara N, Germinario RJ, Bilan PJ, and 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.
Review Articles
- Kewalramani G, Bilan PJ, Klip A: (2010) Muscle insulin resistance: assault by lipids, cytokines and local macrophages. Curr. Opin. Clin. Nutr. Metab. Care, 13: 382-90.
- Ishikura S, Antonescu CN, Klip A: (2010) Documenting GLUT4 exocytosis and endocytosis in muscle cell monolayers. Curr. Protoc. Cell Biol., 46: Unit 15.15: 1-9.
- Bilan PJ, Samokhvalov V, Koshkina A, Schertzer JD, Samaan CM, Klip A: (2009) Direct and macrophage-mediated actions of fatty acids causing insulin resistance in muscle cells. Arch. Physiol. Biochem., 115: 4: 176-90.
- Klip A: (2009) The many ways to regulate glucose transporter 4. Appl. Physiol. Nutr. Metab., 34: 481-7.
- Klip A, Schertzer JD, Bilan PJ, Thong F, Antonescu C: (2009) Regulation of glucose transporter 4 traffic by energy deprivation from mitochondrial compromise. Acta Physiol., 196: 1: 27-35.
- Antonescu CN, Foti M, Sauvonnet N, Klip A: (2009) Ready, set, internalize: mechanisms and regulation of GLUT4 endocytosis. Biosci. Rep., 29: 1: 1-11.
- Antonescu CN, Randhawa VK, Klip A: (2008) Dissecting GLUT4 traffic components in L6 myocytes by fluorescence-based, single-cell assays. Meth. Mol. Biol., Membrane Trafficking, Vancura A (Editor), Humana Press, Totowa, New Jersey, 457: 367-78.
- Samaan MC, Klip A: (2008) Obesity, insulin resistance, and type 2 diabetes: the fat-muscle connection. Endocrinology Rounds (As presented in the Rounds of the Division of Endocrinology and Metabolism, St. Michael’s Hospital), 8: 1-6.
- Zaid H, Antonescu CN, Randhawa VK, and Klip A: (2008) Insulin action on glucose transporters through molecular switches, tracks and tethers. Biochem. J., 413: 201-15.
- Ishikura S, Koshkina A, and Klip A: (2008) Small G proteins in insulin action: Rab and Rho families at the crossroads of signal transduction and GLUT4 vesicle traffic. Acta Physiol., 192: 61-74.
- Dugani CB, and Klip A: (2005) Glucose transporter 4: cycling, compartments and controversies. EMBO Reports, 6: 1137-42.
- Ishiki M, and Klip A: (2005) Minireview: Recent developments in the regulation of glucose transporter-4 traffic: new signals, locations, and partners. Endocrinol., 146: 5071-8.
- Thong FSL, Dugani CB, and Klip A: (2005) Turning signals on and off: GLUT4 traffic in the insulin-signalling highway. Physiol., 20: 271-84.
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