Professor Guy A Rutter

Job Title: Professor and Head of Section of Cell Biology

Research: Signal transduction in the pancreatic β-cell in health and disease

Brief Biosketch: After a PhD in Bristol concerned with signalling by insulin and Ca²⁺-mobilizing hormones, I turned my attention to the pancreatic β-cell with an MRC travelling Fellowship to work with Claes Wollheim in Geneva in 1991. This led to fundamental observations on the metabolic configuration of the β cell. I returned to Bristol in 1993 where I was awarded a HEFCE lectureship in 1995. I established a lab interested in β cell biology, combining  single cell imaging and molecular approaches. These were later extended to the use of mouse models, and to the exploitation of human genetic data as a “feeder” to provide a deeper understanding of the mechanisms through which glucose and other nutrients regulate β-cell gene expression and function. Such insights are likely to provide new ways of treating all forms of type diabetes mellitus, a disease affecting ~ 5% of the world's population.

I was recruited to Imperial College London in 2006 as Head of a new Section of Cell Biology. An important goal currently is to exploit the identification of genes associated in whole genome studies as associated with Type 2 diabetes to provide insights into the control of β-cell mass and function.

Prizes and Awards. I was awarded the Minkowski Prize of the European Association for the Study of Diabetes in 2004 and the Juvenile Diabetes Research Foundation's Mary Jane Krugel Award in 2005.  This year I was the recipient of a Royal Society Wolfson Research Merit Award.

http://www2.imperial.ac.uk/blog/reporter/2011/05/18/wolfson-awards/

 

Recent Publications

Noordeen, N.A., Meur, G., Rutter, G.A.* and Leclerc, I. Glucose-induced nuclear shuttling of ChREBP is mediated by sorcin and Ca²⁺ ions. Diabetes  In press (2011) * Co-corresponding author

Semplici, F., Vaxillaire, M., Fogarty, S., Semach, M., Bonnefond, A., Fontes, G., Philippe, J., Meur, G., Diraison, F., Sessions, R.B., Rutter, J., Poitout, V., Froguel, P, and Rutter, G.A. A human mutation within the per-ARNT-sim (Pas) domain-containing protein kinase (PASK) causes basal insulin hypersecretion. J Biol Chem In press (2011)

Li, D., Chen, S., Bellomo, E.A., Tarasov, A.I., Kaut, C., Rutter, G.A. and Li, W.H. Imaging dynamic insulin release using a fluorescent zinc probe, ZIMIR. Proc Natl Acad Sci In press (2011)

Pullen, T.J., da Silva Xavier, G., Kelsey, G., Rutter, G.A. miR-29a and miR-29b contribute to pancreatic beta-cell specific silencing of Monocarobxylate Transporter 1 (Mct1/slc16a1).  Mol Cell Biol Epub Jun 6 (2011)  PMID: 21646425

Bellomo, E.A., Meur, G., Rutter, G.A. Glucose regulates free cytosolic Zn2⁺ concentration, Slc39 (ZiP) and metallothionein gene expression in primary pancreatic islet beta-cells.  J Biol Chem Epub May 25 (2011)  PMID: 21613223

Meur, G., et al Rutter G.A. Nuclear-cytosolic shuttling of FoxO1 directly regulates mouse Ins2 but not Ins1 gene expression in pancreatic beta cells (MIN6). J Biol. Chem Apr 15; 286(15):13647-56 Epub Feb 18 (2011)  PMID: 21335550

da Silva Xavier, G., Farhan, H., Kim, H., Caxaria, S., Johnson, P. Hughes, S., Bugliani, M., Marselli, L, Marchetti, P., Birzele, F., Sun, G. Scharfmann, R., Rutter, J., Siniakowicz, K., Weir, G., Parker, H. Reimann, F., Gribble, F.M., Rutter, G.A. Per-arnt-sim (PAS) domain-containing protein kinase is downregulated in human islets in type 2 diabetes and regulates glucagon secretion.  Diabetologia Apr; 54 (4): 819-27 Epub Dec 23 2010 (2011) PMID: 21181396

Dominguez, V., Raimondi, C., Somanath, S., Bugliani, M., Loder, M.K., Edling, C.E., Divecha, N., da Silva Xavier, G., Marselli, L., Persaud, S.J., Turner, M.D., Rutter, G.A., Marchetti, P., Falasca, M., Maffucci, T.  Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells  J Biol Chem Feb 11; 286(6):4216-25 Epub Dec 2 (2010) PMID: 21127054 

da Silva Xaiver, G., Sun, G., Qian, Q, Rutter, G.A. and Leclerc, I. ChREBP regulates Pdx-1 and other glucose-sensitive genes in pancreatic β-cells. Biochem Biophys Res Comm  Nov 12; 402(2):252-7 Epub Oct 11 (2010)

Lam CK, Chari, M., Rutter, G.A. and Lam TK. Hypothalamic nutrient sensing activates forebrain-hindbrain neuronal circuits to regulate glucose production in vivo. Diabetes  Jan; 60(1):107-13 Epub Sep 24 (2010)

Leclerc, I., Sun, G., Morris, C., Fernandez-Millan, E., Nyerinda, M., Rutter, G.A. AMP-activated protein kinase regulates glucagon secretion from pancreatic alpha cells. Diabetologia 54(1):125-34  Epub Oct 13 (2010)  PMID: 20938634

Yang,C.S., Lam, C.K.L., Chari, M., Cheung, G.W.C., Kokorovic, A.K., Sun, G., Leclerc, I., Rutter, G.A., Lam, T.K.  Hypothalamic AMPK regulates glucose production. Diabetes  Oct; 59(10):2435-43 Epub Aug 3 (2010) PMID: 20682691

An R., da Silva Xavier G., Semplici F., Vakhshouri S., Hao H.X,. Rutter J., Pagano M.A., Meggio F., Pinna L.A., Rutter G.A.  Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-269 is HIPK2-dependent and affects PDX1 subnuclear localization Biochem Biophys Res Commun Aug 20;399(2):155-61 Epub Jul 15 (2010) PMID: 20637728

MBaya, E., Oules, B., Caspersen, C., Tacine, R., Munnich, A., Rotig, A., Rizzuto, R., Rutter, G.A., Paterlini-Brechot, P., and Chami, M. Regulation of calcium signaling-dependent bioenergetics in mitochondrial respiratory chain complex II deficiency. Cell Death Diff.  Dec;17(12):1855-66 Epub May 21 (2010) PMID: 20489732

Wijesekara N, Dai FF, Hardy AB, Giglou PR, Bhattacharjee A, Koshkin V, Chimienti F, Gaisano HY, Rutter GA, Wheeler MB. Beta cell-specific ZnT8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion.  Diabetologia 53(8):1656-68 Epub Apr 28 (2010)  PMID: 20424817

Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion.

Sun G, Tarasov AI, McGinty JA, French PM, McDonald A, Leclerc I, Rutter GA.  LKB1 deletion with the RIP.Cre-transgene modifies pancreatic {beta}-cell morphology and enhances insulin secretion in vivo.  Am J Physiol Endocrinol Metab, 298 (6): E1261-73 Epub Mar 30 (2010) PMID: 20354156

LKB1 deletion with the RIP.Cre-transgene modifies pancreatic {beta}-cell morphology and enhances insulin secretion in vivo.

Ravier, M.A., Rutter, G.A. Isolation and culture of mouse pancreatic islets for ex vivo imaging studies with trappable or recombinant fluorescent probes.  Methods Mol Biol 633: 171-84 (2010) PMID: 20204627

Voronina, S.G., Barrow, S.L., Simpson, A.W., Gerasimenko, O.V., da Silva Xavier, G., Rutter, G.A. Petersen, O.H., and Tepikin, A.V. Dynamic changes in cytosolic and mitochondrial ATP levels in pancreatic acinar cells. Gastroenterology, 138(5):1976-87 Epub Jan 25 (2010)  PMID: 20102715

Sun, G., Tarasov, A.I., McGinty, J., McDonald, A., daSilvaXavier, G., Gorman, T., Marley, A., French, P.M., Parker, H., Gribble, F., Reimann, F., Viollet, B., Leclerc, I., Rutter, G.A. Ablation of AMPKα1 and α2 from pancreatic beta cells and RIP.Cre neurons suppresses insulin release in vivo. Diabetologia, 53 (5) 924-36 Epub Mar 11 (2010) PMID: 20221584

Pullen, T.J., Khan, AM., Barton, G., Sun., G., and Rutter, G.A. Identification of genes selectively disallowed in the pancreatic islet. Islets, 2(2), 89-95 (2010)  PMID: 21099300

Noordeen, N., Khera, T.K., Sun, G., Longbottom, E.R., da Silva Xavier, G., Rutter, G.A., Leclerc, I., ChREBP is a negative regulator of ARNT/HIF-1β gene expression in pancreatic islet β-cells. Diabetes 59 (1): 153-60 Epub Oct 15 2009 (2010)  PMID: 19833882

Meur, G., Simon, A., Harun, N., Dechaume, A., Bonneford, A., Virally, M., Fetita, S., Tarasov, A.I., Boesgaard, T.W., Pedersen, O., Hansen, T., Polak, M., Gautier, J-F, Froguel, P., Rutter, G. A., Vaxillaire, M. Insulin gene mutations resulting in a MODY phenotype: marked differences in clinical presentation, metabolic status and pathogenic effect through ER retention. Diabetes, 59(3): 653-61 Epub Dec 10 (2009)

Vinkenborg, J.L., Bellomo, E.A., Nicolson, T.J., Koay, M.S., Merkx, M. Rutter, G.A. Accurate measurement of cytosolic free zinc concentration using eCALWY variants: a toolbox of genetically encoded FRET sensors. Nature Protocols, 6: 737-740 (2009)  http://www/natureprotocols.com/2009///accurate_measurement_of_cytoso.php                                                                                                                                  

Vinkenborg, J.L., Nicolson, T.J., Bellomo, E.A., Koay, M.S., Rutter, G.A.* Merkx, M. Genetically-encoded FRET sensors to monitor Zn²⁺ homeostasis in living cells. Nature Methods  6(10):737-40 Epub Aug 30 (2009) *corresponding author http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.1368.html

McDonald, A., Fogarty, S., Leclerc, I., Hill, E., Hardie, D.G., and Rutter, G.A. Control of insulin granule dynamics by AMPK-dependent KLC1 phosphorylation. Islets 1(3):1-11 (2009)

Lemaire, K., Ravier, M.A., Chimienti, F., Rutter G.A., Gilon, P., Veld, P. Schuit, F.  Insulin crystallisation depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice. Proc Natl Acad Sci, 106  (35): 14872-14877 Epub Aug 18 (2009)   http://www.pnas.org/content/106/35/14872.full

Lerner, R.G., Depatie, C. Rutter G.A., Screaton R., Balthasar, N.  A role for the CREB coactivator TORC2 in the hypothalamic mechanisms linking glucose-sensing with gene regulation.  Embo Rep 10(10):1175-81 Epub Aug 28 (2009) http://www.nature.com/embor/journal/vaop/ncurrent/full/embor2009177.html

Nicolson, T.J., Bellomo, E.A., Wijesekara, N., Loder, M.K., Baldwin, J.M., Gyulkhandanyan, A.V., Koshin, V., Tarasov, A.I., Carzaniga, R., Kronenberger, K., Taneja, T.K., da Silva Xavier, G., Libert, S., Froguel, P., Scharfmann, R., Stetsyuk, V., Ravassard, P., Parker, H., Gribble, F.M., Reimann, F., Sladek, R., Hughes, S.J., Johnson, P.R.V., Massebouef, M., Burcelin, R. Baldwin, S.A., Liu, M.m Lara-Lemus, R., Arvan, P., Schuit, F.C., Wheler, M.B., Chiemienti, F., Rutter, G.A. Insulin storage and glucose homeostasis in mice null for the granuel zinc transporter ZnT8 and studies of the type 2 diabetes-associated varients Diabetes, 58(9):2070-83 Epub Jun 19(2009) http://diabetes.diabetesjournals.org/content/58/9/2070.full

Rutter group publications

Research Support. Supported by Programme and other grants from the Wellcome Trust, MRC, DUK, JDRF, BBSRC, NIH, BHF and EU.

 

Related link to Section of Cell Biology

 http://www1.imperial.ac.uk/medicine/about/divisions/departmentofmedicine/diabetesendocrinologymetabolism/cellbiology/