Calum Sutherland

+44 (0)1382 383098
Professor of Molecular Medicine

Bio

Biography

Career: Dr Sutherland has worked in industry with Glaxo Group Research, obtained his PhD under the supervision of Professor Sir Philip Cohen, at the University of Dundee, and studied under Professor Daryl K Granner, at Vanderbilt University, Tennessee. He has obtained personal Fellowships from the American Diabetes Association, the Wellcome Trust and Diabetes UK covering his work from 1994 to 2008. He has obtained personal research funding in excess of £10 million and contributes to undergraduate teaching in Life Sciences and the Medical Faculty.

Overview: The Sutherland lab has contributed to the understanding of insulin signalling mechanisms and regulation of gene transcription, most recently in human tissue. Major breakthroughs include establishing a major regulatory mechanism of the key protein kinase GSK3, demonstrating that GSK3 inhibition enhances insulin action in the liver and is a potential treatment for diabetes, identifying the signalling pathway by which insulin turns off hepatic glucose production, finding the mechanism by which the protein CRMP2 is modified to promote its accumulation into tangles in Alzheimer’s disease and finding new physiological functions for GSK3 and the CRMP family of proteins.

Current Focus: The lab continues to develop technology for the discovery of insulin sensitising drugs and biomarkers of metabolic dysfunction that would help identify people at high risk of developing Type 2 Diabetes and dementia. In recent years the lab has characterised molecular connections between Diabetes and Dementia that could explain the increased risk of Dementia in the diabetic population, and is investigating the impact of insulin resistance and obesity on heart disease, cancer, behaviour and the effectiveness of diabetes therapies.

Research

Diabetes and Dementia

Funding: Diabetes UK and MRC

Insulin is the major hormone that prevents hyperglycemia after a meal. When insulin does not work properly prolonged hyperglycemia occurs (Diabetes), resulting in increased risk of heart disease, blindness, kidney failure, amputation, dementia and stroke.  There are now more than 2 million people in the UK with diabetes. An understanding of the molecular aspects of insulin action will allow us to understand why diabetes occurs and how to develop strategies for prevention and cure, as well as prevent the complications of the disease. For example, insulin regulates the enzyme GSK3, which is closely linked to molecular development of neurodegenerative diseases such as Alzheimer's disease. Our group currently studies three aspects of insulin action.

1) Obesity, insulin resistance and molecular disease. In collaboration with our clinical colleagues at Ninewells Medical School we are establishing whether any of the molecules known to be important in the insulin regulation of gene expression are improperly regulated in human insulin resistance. This work led to the discovery of a novel insulin signalling mechanismThe human studies are generating new information on potential ‘biomarkers’ of early progression to diabetes, which should allow earlier and more efficacious intervention. In addition we are investigating whether obesity alters the activity of CDK5, and how that alters response to drugs used in diabetes. In particular we are establishing whether changes in CDK5 activity may underpin some of the increased risk of cancer in the obese population.

2) Insulin action and the brain. Perhaps surprisingly, insulin receptors are found throughout the brain. Interestingly, there is a higher incidence of Alzheimer’s disease in the diabetic population and it is proposed to be due to defective insulin action on the brain. We have identified a family of proteins regulated by insulin and shown that it is dysregulated in Alzheimer’s disease 13. These proteins (CRMPs) are targeted by GSK3 which is known to be upregulated in diabetes 14-16. Therefore abnormal activity of this family could explain part of the association between diabetes and Alzheimer’s disease. In collaboration with Professor Balfour and Dr Stewart at Ninewells we have identified a specific overnutrition-induced change in behavioural flexibility that is not prevented by the anti-diabetes drug metformin 17 18. In addition we are studying a new function of GSK3, the coordinated control of protein stability. This function provides the opportunity to develop new biomarkers of GSK3 which could have clinical utlity in the early diagnosis of dementia, as well as the molecular stratification of diabetes (to improve treatment and care).

 

3) The genetic contribution to drug response in diabetes. In collaboration with Professor Pearson and McCrimmon at Ninewells we are studying the biology behind the genetic contribution to response to the most common anti-diabetes therapy, metformin. We are investigating why gentic variation in 3 genes influences whether a person with diabetes would repsond to metformin and improve their blood glucose. The hope is this information will improve prescribing practice in diabetes, and may help find new therapies for those that can't use metformin.

Publications

Robertson, H, Hayes, JD & Sutherland, C 2018,

'A partnership with the proteasome: the destructive nature of GSK3' Biochemical Pharmacology, vol. 147, pp. 77-92.
https://doi.org/10.1016/j.bcp.2017.10.016

Research output: Contribution To Journal



Logie, L, Van Aalten, L, Knebel, A, Force, T, Hastie, CJ, Mac Lauchlan, H, Campbell, DG, Gourlay, R, Prescott, A, Davidson, J, Fuller, W & Sutherland, C 2017,

'Rab-GTPase binding effector protein 2 (RABEP2) is a primed substrate for Glycogen Synthase kinase-3 (GSK3)' Scientific Reports, vol. 7, 17682.
https://doi.org/10.1038/s41598-017-17087-6

Research output: Contribution To Journal



Davidson, J, Mc Donald, TJ, Sutherland, C, Mostazir, M, Van Aalten, L & Wilkin, TJ 2017,

'Proinsulin is stable at room temperature for 24 hours in EDTA: A clinical laboratory analysis (ad APT 3)' PLo S ONE, vol. 12, no. 4, e0171716, pp. 1-6.
https://doi.org/10.1371/journal.pone.0171716

Research output: Contribution To Journal



Mc Neilly, AD, Gao, A, Hill, AY, Gomersall, T, Balfour, DJK, Sutherland, C & Stewart, CA 2016,

'The effect of dietary intervention on the metabolic and behavioural impairments generated by short term high fat feeding in the rat' Physiology & Behavior, vol. 167, pp. 100-109.
https://doi.org/10.1016/j.physbeh.2016.08.035

Research output: Contribution To Journal



Hayes, JD, Ebisine, K, Sharma, RS, Chowdhry, S, Dinkova-Kostova, AT & Sutherland, C 2016,

'Regulation of the CNC-b ZIP transcription factor Nrf2 by Keap1 and the axis between GSK-3 and β-Tr CP' Current Opinion in Toxicology, vol. 1, pp. 92-103.
https://doi.org/10.1016/j.cotox.2016.10.003

Research output: Contribution To Journal



Dayalan Naidu, S, Sutherland, C, Zhang, Y, Risco, A, de la Vega, L, Caunt, CJ, Hastie, CJ, Lamont, DJ, Torrente, L, Chowdhry, S, Benjamin, IJ, Keyse, SM, Cuenda, A & Dinkova-Kostova, AT 2016,

'Heat Shock Factor 1 is a Substrate for p38 Mitogen-Activated Protein Kinases' Molecular and Cellular Biology, vol. 36, no. 18, pp. 2403-2417.
https://doi.org/10.1128/MCB.00292-16

Research output: Contribution To Journal



Zhou, K, Yee, SW, Seiser, EL, van Leeuwen, N, Tavendale, R, Bennett, AJ, Groves, CJ, Coleman, RL, van der Heijden, AA, Beulens, JW, de Keyser, CE, Zaharenko, L, Rotroff, DM, Out, M, Jablonski, KA, Chen, L, Javorský, M, Židzik, J, Levin, AM, Williams, LK, Dujic, T, Semiz, S, Kubo, M, Chien, H-C, Maeda, S, Witte, JS, Wu, L, Tkáč, I, Kooy, A, van Schaik, RHN, Stehouwer, CDA, Logie, L, Sutherland, C, Klovins, J, Pirags, V, Hofman, A, Stricker, BH, Motsinger-Reif, AA, Wagner, MJ, Innocenti, F, Hart, LM, Holman, RR, Mc Carthy, MI, Hedderson, MM, Palmer, CNA, Florez, JC, Giacomini, KM, Pearson, ER & Met Gen Investigators 2016,

'Variation in the Glucose Transporter gene SLC2A2 is associated with glycaemic response to metformin' Nature Genetics, vol. 48, no. 9, pp. 1055-1059.
https://doi.org/10.1038/ng.3632

Research output: Contribution To Journal



Cameron, A, Logie, L, Patel, K, Bacon, S, Forteath, C, Harthill, J, Roberts, A, Sutherland, C, Stewart, D, Viollet, B, Sakamoto, K, Mc Dougall, G, Foretz, M & Rena, G 2016,

'Investigation of salicylate hepatic responses in comparison with chemical analogues of the drug' Biochimica et Biophysica Acta. Molecular Basis of Disease, vol. 1862, no. 8, pp. 1412-1422.
https://doi.org/10.1016/j.bbadis.2016.04.015

Research output: Contribution To Journal



Grant, NJ, Coates, PJ, Woods, YL, Bray, SE, Morrice, NA, Hastie, CJ, Lamont, DJ, Carey, FA & Sutherland, C 2015,

'Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis' BMC Cancer, vol. 15, 885.
https://doi.org/10.1186/s12885-015-1691-1

Research output: Contribution To Journal



Balastik, M, Zhou, XZ, Alberich-Jorda, M, Weissova, R, Žiak, J, Pazyra-Murphy, MF, Cosker, KE, Machonova, O, Kozmikova, I, Chen, C-H, Pastorino, L, Asara, JM, Cole, A, Sutherland, C, Segal, RA & Lu, KP 2015,

'Prolyl isomerase Pin1 regulates axon guidance by stabilizing CRMP2A selectively in distal axons' Cell Reports, vol. 13, no. 4, pp. 812-828.
https://doi.org/10.1016/j.celrep.2015.09.026

Research output: Contribution To Journal



Hayes, JD, Chowdhry, S, Dinkova-Kostova, AT & Sutherland, C 2015,

'Dual regulation of transcription factor Nrf2 by Keap1 and by the combined actions of β-Tr CP and GSK-3' Biochemical Society Transactions, vol. 43, no. 4, pp. 611-620.
https://doi.org/10.1042/BST20150011

Research output: Contribution To Journal



Sutherland, C & Duthie, AC 2015,

'Invited commentary on … Lithium treatment and risk for dementia in adults with bipolar disorder' British Journal of Psychiatry, vol. 207, no. 1, pp. 52-54.
https://doi.org/10.1192/bjp.bp.114.161729

Research output: Contribution To Journal



Holland, PR, Pannozzo, MA, Bastin, ME, Mc Neilly, AD, Ferguson, KJ, Caughey, S, Jansen, MA, Merrifield, GD, Marshall, I, Mullins, JJ, Wardlaw, JM, Sutherland, C & Horsburgh, K 2015,

'Hypertension fails to disrupt white matter integrity in young or aged Fisher (F44) Cyp1a1Ren2 transgenic rats' Journal of Cerebral Blood Flow and Metabolism, vol. 35, no. 2, pp. 188-192.
https://doi.org/10.1038/jcbfm.2014.201

Research output: Contribution To Journal



Mc Neilly, AD, Stewart, CA, Sutherland, C & Balfour, DJK 2015,

'High fat feeding is associated with stimulation of the hypothalamic-pituitary-adrenal axis and reduced anxiety in the rat' Psychoneuroendocrinology, vol. 52, pp. 272-280.
https://doi.org/10.1016/j.psyneuen.2014.12.002

Research output: Contribution To Journal



Patel, K, Foretz, M, Marion, A, Campbell, DG, Gourlay, R, Boudaba, N, Tournier, E, Titchenell, P, Peggie, M, Deak, M, Wan, M, Kaestner, KH, Göransson, O, Viollet, B, Gray, NS, Birnbaum, MJ, Sutherland, C & Sakamoto, K 2014,

'The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver' Nature Communications, vol. 5, 4535.
https://doi.org/10.1038/ncomms5535

Research output: Contribution To Journal



Liz, MA, Mar, FM, Santos, TE, Pimentel, HI, Marques, AM, Morgado, MM, Vieira, S, Sousa, VF, Pemble, H, Wittmann, T, Sutherland, C, Woodgett, JR & Sousa, MM 2014,

'Neuronal deletion of GSK3beta increases microtubule speed in the growth cone and enhances axon regeneration via CRMP-2 and independently of MAP1B and CLASP2' BMC Biology, vol. 12, 47.
https://doi.org/10.1186/1741-7007-12-47

Research output: Contribution To Journal



Xia, C, Nguyen, M, Garrison, AK, Zhao, Z, Wang, Z, Sutherland, C & Ma, L 2013,

'CNP/c GMP signaling regulates axon branching and growth by modulating microtubule polymerization' Developmental Neurobiology, vol. 73, no. 9, pp. 673-687.
https://doi.org/10.1002/dneu.22078

Research output: Contribution To Journal



Patel, K, Goransson, O, Sutherland, C & Sakamoto, K 2013,

'Hormonal regulation of the Salt-inducible Kinase (SIK), a key mediator that controls hepatic gluconeogenesis' Diabetic Medicine, vol. 30, no. Suppl. 1, P577, pp. E2-E2.
https://doi.org/10.1111/dme.12170

Research output: Contribution To Journal



Patel, K, Goransson, O, Sutherland, C & Sakamoto, K 2013,

'Hormonal regulation of the Salt-inducible Kinase (SIK), a key mediator that controls hepatic gluconeogenesis' Diabetes UK Professional Conference 2013, Manchester, United Kingdom, 13/03/13 - 15/03/13, .

Research output: Contribution To Conference



Ruiz-Alcaraz, AJ, Lipina, C, Petrie, JR, Murphy, MJ, Morris, AD, Sutherland, C & Cuthbertson, DJ 2013,

'Obesity-Induced Insulin Resistance in Human Skeletal Muscle Is Characterised by Defective Activation of p42/p44 MAP Kinase' PLo S ONE, vol. 8, no. 2, e56928.
https://doi.org/10.1371/journal.pone.0056928

Research output: Contribution To Journal



Mc Neilly, AD, Williamson, R, Balfour, DJK, Stewart, CA & Sutherland, C 2013,

'Erratum to: A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin' Diabetologia, vol. 56, no. 1, pp. 230.
https://doi.org/10.1007/s00125-012-2761-4

Research output: Contribution To Journal



Mc Neilly, AD, Williamson, R, Balfour, DJK, Stewart, CA & Sutherland, C 2012,

'A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin' Diabetologia, vol. 55, no. 11, pp. 3061-3070.
https://doi.org/10.1007/s00125-012-2686-y

Research output: Contribution To Journal



Williamson, R, Mc Neilly, A & Sutherland, C 2012,

'Insulin resistance in the brain: An old-age or new-age problem?' Biochemical Pharmacology, vol. 84, no. 6, pp. 737-45.
https://doi.org/10.1016/j.bcp.2012.05.007

Research output: Contribution To Journal



Zhou, K, Bellenguez, C, Sutherland, C, Hardie, G, Palmer, C, Donnelly, P & Pearson, E 2012,

'The role of ATM in response to metformin treatment and activation of AMPK reply' Nature Genetics, vol. 44, no. 4, pp. 361-362.
https://doi.org/10.1038/ng.2234

Research output: Contribution To Journal



Schofield, CJ & Sutherland, C 2012,

'Disordered insulin secretion in the development of insulin resistance and Type 2 diabetes' Diabetic Medicine, vol. 29, no. 8, pp. 972-979.
https://doi.org/10.1111/j.1464-5491.2012.03655.x

Research output: Contribution To Journal



Chowdhry, S, Zhang, Y, Mc Mahon, M, Sutherland, C, Cuadrado, A & Hayes, JD 2012,

'Nrf2 is controlled by two distinct β-Tr CP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity' Oncogene, vol. 32, pp. 3765-3781.
https://doi.org/10.1038/onc.2012.388

Research output: Contribution To Journal



Graham, L & Sutherland, C 2011,

'Models of Dementia: an introductory overview' Biochemical Society Transactions, vol. 39, pp. 851-856.
https://doi.org/10.1042/BST0390851

Research output: Contribution To Journal



Farghaian, H, Turnley, AM, Sutherland, C & Cole, AR 2011,

'Bioinformatic Prediction and Confirmation of beta-Adducin as a Novel Substrate of Glycogen Synthase Kinase 3' Journal of Biological Chemistry, vol. 286, no. 28, pp. 25274-25283.
https://doi.org/10.1074/jbc.M111.251629

Research output: Contribution To Journal



Astle, MV, Ooms, LM, Cole, AR, Binge, LC, Dyson, JM, Layton, MJ, Petratos, S, Sutherland, C & Mitchell, CA 2011,

'Identification of a Proline-rich Inositol Polyphosphate 5-Phosphatase (PIPP)center dot Collapsin Response Mediator Protein 2 (CRMP2) Complex That Regulates Neurite Elongation' Journal of Biological Chemistry, vol. 286, no. 26, pp. 23407-23418.
https://doi.org/10.1074/jbc.M110.214247

Research output: Contribution To Journal



Petrie, JR, Pearson, ER & Sutherland, C 2011,

'Implications of genome wide association studies for the understanding of type 2 diabetes pathophysiology' Biochemical Pharmacology, vol. 81, no. 4, pp. 471-477.
https://doi.org/10.1016/j.bcp.2010.11.010

Research output: Contribution To Journal



Mc Neilly, AD, Williamson, R, Sutherland, C, Balfour, DJK & Stewart, CA 2011,

'High fat feeding promotes simultaneous decline in insulin sensitivity and cognitive performance in a delayed matching and non-matching to position task' Behavioural Brain Research, vol. 217, no. 1, pp. 134-141.
https://doi.org/10.1016/j.bbr.2010.10.017

Research output: Contribution To Journal



Zhou, K, Bellenguez, C, Spencer, CCA, Bennett, AJ, Coleman, RL, Tavendale, R, Hawley, SA, Donnelly, LA, Schofield, C, Groves, CJ, Burch, L, Carr, F, Strange, A, Freeman, C, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Craddock, N, Deloukas, P, Dronov, S, Duncanson, A, Edkins, S, Gray, E, Hunt, S, Jankowski, J, Langford, C, Markus, HS, Mathew, CG, Plomin, R, Rautanen, A, Sawcer, SJ, Samani, NJ, Trembath, R, Viswanathan, AC, Wood, NW, Harries, LW, Hattersley, AT, Doney, ASF, Colhoun, H, Morris, AD, Sutherland, C, Hardie, DG, Peltonen, L, Mc Carthy, MI, Holman, RR, Palmer, CNA, Donnelly, P, Pearson, ER & Wellcome Trust Case Control Consor, Go DARTS UKPDS Diabet Pharmacogenet, MAGIC Investigators 2011,

'Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes' Nature Genetics, vol. 43, no. 2, pp. 117-120.
https://doi.org/10.1038/ng.735

Research output: Contribution To Journal



Williamson, R, van Aalten, L, Mann, DMA, Platt, B, Plattner, F, Bedford, L, Mayer, J, Howlett, D, Usardi, A, Sutherland, C & Cole, AR 2011,

'CRMP2 Hyperphosphorylation is Characteristic of Alzheimer's Disease and not a Feature Common to Other Neurodegenerative Diseases' Journal of Alzheimer's Disease, vol. 27, no. 3, pp. 615-625.
https://doi.org/10.3233/JAD-2011-110617

Research output: Contribution To Journal



Sutherland, C 2011,

'What are the bona fide GSK3 substrates?' International Journal of Alzheimer's Disease, vol. 2011, pp. 1-23.
https://doi.org/10.4061/2011/505607

Research output: Contribution To Journal



Kickstein, E, Krauss, S, Thornhill, P, Rutschow, D, Zeller, R, Sharkey, J, Williamson, R, Fuchs, M, Koehler, A, Glossmann, H, Schneider, R, Sutherland, C & Schweiger, S 2010,

'Biguanide metformin acts on tau phosphorylation via m TOR/protein phosphatase 2A (PP2A) signaling' Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 50, pp. 21830-21835.
https://doi.org/10.1073/pnas.0912793107

Research output: Contribution To Journal



Lyn-Adams, C, Frenguelli, B, Moffat, K & Sutherland, C 2010,

'Regulation of Tau-Dependent Toxicity by Brain Selective/SAD Kinases' Journal of Neurogenetics, vol. 24, pp. 12-12.
https://doi.org/10.3109/01677063.2011.534918

Research output: Contribution To Journal



Soutar, MPM, Kim, W-Y, Williamson, R, Peggie, M, Hastie, CJ, Mc Lauchlan, H, Snider, WD, Gordon-Weeks, PR & Sutherland, C 2010,

'Evidence that glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain' Journal of Neurochemistry, vol. 115, no. 4, pp. 974-983.
https://doi.org/10.1111/j.1471-4159.2010.06988.x

Research output: Contribution To Journal



Logie, L, Ruiz-Alcaraz, AJ, Schofield, CJ, Hundal, HS, Feuerstein, GZ, Brady, JD, Crowther, D, Tommasi, AM, Grierson, CE, Shepherd, B, Morris, AD, Hansen, MK, Pearson, E & Sutherland, C 2010,

'Generation, validation and humanisation of a novel insulin resistant cell model' Biochemical Pharmacology, vol. 80, no. 7, pp. 1042-1049.
https://doi.org/10.1016/j.bcp.2010.06.011

Research output: Contribution To Journal



Clayton, EL, Sue, N, Smillie, KJ, O'Leary, T, Bache, N, Cheung, G, Cole, AR, Wyllie, DJ, Sutherland, C, Robinson, PJ & Cousin, MA 2010,

'Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles' Nature Neuroscience, vol. 13, no. 7, pp. 845-U85.
https://doi.org/10.1038/nn.2571

Research output: Contribution To Journal



Alabed, YZ, Pool, M, Tone, SO, Sutherland, C & Fournier, AE 2010,

'GSK3 beta Regulates Myelin-Dependent Axon Outgrowth Inhibition through CRMP4' Journal of Neuroscience, vol. 30, no. 16, pp. 5635-5643.
https://doi.org/10.1523/JNEUROSCI.6154-09.2010

Research output: Contribution To Journal



Lyn-Adams, C, Moffat, K, Sutherland, C & Frenguelli, BG 2010,

'All tangled up: tau-dependent neurodegeneration' Biochemist, vol. 32, no. 2, pp. 10-13.

Research output: Contribution To Journal



Woods, YL, Petrie, JR & Sutherland, C 2009,

'Dissecting insulin signaling pathways: individualised therapeutic targets for diagnosis and treatment of insulin resistant states' Endocrine, Metabolic and Immune Disorders - Drug Targets, vol. 9, no. 2, pp. 187-198.
https://doi.org/10.2174/187153009788452408

Research output: Contribution To Journal



Soutar, MPM, Thornhill, P, Cole, AR & Sutherland, C 2009,

'Increased CRMP2 Phosphorylation is Observed in Alzheimer's Disease: Does this Tell us Anything About Disease Development?' Current Alzheimer Research, vol. 6, no. 3, pp. 269-278.
https://doi.org/10.2174/156720509788486572

Research output: Contribution To Journal



Sandilands, A, Sutherland, C, Irvine, AD & Mc Lean, WHI 2009,

'Filaggrin in the frontline: role in skin barrier function and disease' Journal of Cell Science, vol. 122, no. 9, pp. 1285-1294.
https://doi.org/10.1242/jcs.033969

Research output: Contribution To Journal



Babraj, JA, Mustard, K, Sutherland, C, Towler, MC, Chen, S, Smith, K, Green, K, Leese, G, Hardie, DG, Rennie, MJ & Cuthbertson, DJ 2009,

'Blunting of AICAR-induced human skeletal muscle glucose uptake in type 2 diabetes is dependent on age rather than diabetic status' American Journal of Physiology, Endocrinology and Metabolism, vol. 296, no. 5, pp. E1042-E1048.
https://doi.org/10.1152/ajpendo.90811.2008

Research output: Contribution To Journal



Ning, K, Miller, LC, Laidlaw, HA, Watterson, KR, Gallagher, J, Sutherland, C & Ashford, MLJ 2009,

'Leptin-dependent Phosphorylation of PTEN Mediates Actin Restructuring and Activation of ATP-sensitive K+ Channels' Journal of Biological Chemistry, vol. 284, no. 14, pp. 9331-9340.
https://doi.org/10.1074/jbc.M806774200

Research output: Contribution To Journal



Rajkhowa, M, Brett, S, Cuthbertson, DJ, Lipina, C, Ruiz-Alcaraz, AJ, Thomas, GE, Logie, L, Petrie, JR & Sutherland, C 2009,

'Insulin resistance in polycystic ovary syndrome is associated with defective regulation of ERK1/2 by insulin in skeletal muscle in vivo' Biochemical Journal, vol. 418, pp. 665-671.
https://doi.org/10.1042/BJ20082176

Research output: Contribution To Journal



Holscher, C, van Aalten, L & Sutherland, C 2008,

'Anaesthesia generates neuronal insulin resistance by inducing hypothermia' BMC Neuroscience, vol. 9, 100, pp. -.
https://doi.org/10.1186/1471-2202-9-100

Research output: Contribution To Journal



Cole, AR, Soutar, MPM, Rembutsu, M, van Aalten, L, Hastie, CJ, Mclauchlan, H, Peggie, M, Balastik, M, Lu, KP & Sutherland, C 2008,

'Relative resistance of Cdk5-phosphorylated CRMP2 to dephosphorylation' Journal of Biological Chemistry, vol. 283, no. 26, pp. 18227-18237.
https://doi.org/10.1074/jbc.M801645200

Research output: Contribution To Journal



Bayascas, JR, Wullschleger, S, Sakamoto, K, Garcia-Martinez, JM, Clacher, C, Komander, D, van Aalten, DMF, Boini, KM, Lan, F, Lipina, C, Logie, L, Sutherland, C, Chudek, JA, van Diepen, JA, Voshol, PJ, Lucocq, JM & Alessi, DR 2008,

'Mutation of the PDK1 PH domain inhibits protein kinase B/Akt, leading to small size and insulin resistance' Molecular and Cellular Biology, vol. 28, no. 10, pp. 3258-3272.
https://doi.org/10.1128/MCB.02032-07

Research output: Contribution To Journal



Rembutsu, M, Soutar, MPM, Van Aalten, L, Gourlay, R, Hastie, CJ, Mc Lauchlan, H, Morrice, NA, Cole, AR & Sutherland, C 2008,

'Novel procedure to investigate the effect of phosphorylation on protein complex formation in vitro and in cells' Biochemistry, vol. 47, no. 7, pp. 2153-2161.
https://doi.org/10.1021/bi702030w

Research output: Contribution To Journal



Sutherland, C & Ashford, M 2008,

Convergence of leptin and insulin signaling networks in obesity. in J Harvey & DJ Withers (eds), Neurobiology of obesity. Cambridge University Press, Cambridge, pp. 127-163.
https://doi.org/10.1017/CBO9780511541643.006

Research output: Contribution To Book Anthology



Cole, AR & Sutherland, C 2008,

Measuring GSK3 expression and activity in cells. in E Vincan (ed.), Wnt signaling: pathway methods and mammalian models. Methods in Molecular Biology, vol. 468, Humana Press, pp. 45-65.
https://doi.org/10.1007/978-1-59745-249-6_4

Research output: Contribution To Book Anthology



Sutherland, C, O'Brien, RM & Granner, DK 2007,

Insulin action gene regulation. in Mechanisms of Insulin Action: Medical Intelligence Unit. Springer New York, pp. 110-132.
https://doi.org/10.1007/978-0-387-72204-7_6

Research output: Contribution To Book Anthology



Cole, AR, Noble, W, van Aalten, L, Plattner, F, Meimaridou, R, Hogan, D, Taylor, M, La Francois, J, Gunn-Moore, F, Verkhratsky, A, Oddo, S, La Ferla, F, Giese, KP, Dineley, KT, Duff, K, Richardson, JC, Yan, SD, Hanger, DP, Allan, SM & Sutherland, C 2007,

'Collapsin response mediator protein-2 hyperphosphorylation is an early event in Alzheimer's disease progression' Journal of Neurochemistry, vol. 103, no. 3, pp. 1132-1144.
https://doi.org/10.1111/j.1471-4159.2007.04829.x

Research output: Contribution To Journal



Logie, L, Ruiz-Alcaraz, AJ, Keane, M, Woods, YL, Bain, J, Marquez, R, Alessi, DR & Sutherland, C 2007,

'Characterization of a protein kinase B inhibitor in vitro and in insulin-treated liver cells' Diabetes, vol. 56, no. 9, pp. 2218-2227.
https://doi.org/10.2337/db07-0343

Research output: Contribution To Journal



Wishart, TM, Paterson, JM, Short, DM, Meredith, S, Robertson, KA, Sutherland, C, Cousin, MA, Dutia, MB & Gillingwater, TH 2007,

'Differential proteomics analysis of synaptic proteins identifies potential cellular targets and protein mediators of synaptic neuroprotection conferred by the slow Wallerian degeneration (Wld(s)) gene' Molecular & Cellular Proteomics, vol. 6, no. 8, pp. 1318-1330.
https://doi.org/10.1074/mcp.M600457-MCP200

Research output: Contribution To Journal



Cuthbertson, DJ, Babraj, JA, Mustard, KJW, Towler, MC, Green, KA, Wackerhage, H, Leese, GP, Baar, K, Thomason-Hughes, M, Sutherland, C, Hardie, DG & Rennie, MJ 2007,

'5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men' Diabetes, vol. 56, no. 8, pp. 2078-2084.
https://doi.org/10.2337/db06-1716

Research output: Contribution To Journal



Cole, AR, Astell, A, Green, C & Sutherland, C 2007,

'Molecular connexions between dementia and diabetes' Neuroscience and Biobehavioral Reviews, vol. 31, no. 7, pp. 1046-1063.
https://doi.org/10.1016/j.neubiorev.2007.04.004

Research output: Contribution To Journal



Finlay, D, Ruiz-Alcaraz, AJ, Lipina, C, Perrier, S & Sutherland, C 2006,

'A temporal switch in the insulin-signalling pathway that regulates hepatic IGF-binding protein-1 gene expression' Journal of Molecular Endocrinology, vol. 37, no. 2, pp. 227-237.
https://doi.org/10.1677/jme.1.02084

Research output: Contribution To Journal



Cole, AR, Causeret, F, Yadirgi, G, Hastie, CJ, Mclauchlan, H, Mc Manus, EJ, Hernandez, F, Eickholt, BJ, Nikolic, M, Sutherland, C & Sutherland, C 2006,

'Distinct priming kinases contribute to differential regulation of collapsin response mediator proteins by glycogen synthase kinase-3 in vivo' Journal of Biological Chemistry, vol. 281, no. 24, pp. 16591-16598.
https://doi.org/10.1074/jbc.M513344200

Research output: Contribution To Journal



Liu, HK, Perrier, S, Lipina, C, Finlay, D, Mc Lauchlan, H, Hastie, CJ, Hundal, HS, Sutherland, C & Sutherland, C 2006,

'Functional characterisation of the regulation of CAAT enhancer binding protein alpha by GSK-3 phosphorylation of Threonines 222/226' BMC Molecular Biology, vol. 7, 14, pp. -.
https://doi.org/10.1186/1471-2199-7-14

Research output: Contribution To Journal



Ruiz-Alcaraz, AJ, Liu, H-K, Cuthbertson, DJ, Mc Manus, EJ, Akhtar, S, Lipina, C, Morris, AD, Petrie, JR, Hundal, HS & Sutherland, C 2005,

'A novel regulation of IRS1 (insulin receptor substrate-1) expression following short term insulin administration' Biochemical Journal, vol. 392, pp. 345-352.
https://doi.org/10.1042/BJ20051194

Research output: Contribution To Journal



Mac Aulay, K, Blair, AS, Hajduch, E, Terashima, T, Baba, O, Sutherland, C & Hundal, HS 2005,

'Constitutive activation of GSK3 down-regulates glycogen synthase abundance and glycogen deposition in rat skeletal muscle cells' Journal of Biological Chemistry, vol. 280, no. 10, pp. 9509-9518.
https://doi.org/10.1074/jbc.M411648200

Research output: Contribution To Journal



Rencurel, F, Stenhouse, A, Hawley, SA, Friedberg, T, Hardie, DG, Sutherland, C & Wolf, CR 2005,

'AMP-activated protein kinase mediates phenobarbital induction of CYP2B gene expression in hepatocytes and a newly derived human hepatoma cell line' Journal of Biological Chemistry, vol. 280, no. 6, pp. 4367-4373.
https://doi.org/10.1074/jbc.M412711200

Research output: Contribution To Journal



Mora, A, Lipina, C, Tronche, F, Sutherland, C & Alessi, DR 2005,

'Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure' Biochemical Journal, vol. 385, no. 3, pp. 639-648.
https://doi.org/10.1042/BJ20041782

Research output: Contribution To Journal



Lipina, C, Huang, X, Finlay, D, Mc Manus, EJ, Alessi, DR & Sutherland, C 2005,

'Analysis of hepatic gene transcription in mice expressing insulin-insensitive GSK3' Biochemical Journal, vol. 392, no. 3, pp. 633-639.
https://doi.org/10.1042/BJ20051046

Research output: Contribution To Journal



Mirshamsi, S, Laidlaw, HA, Ning, K, Anderson, E, Burgess, LA, Gray, A, Sutherland, C & Ashford, MLJ 2004,

'Leptin and insulin stimulation of signalling pathways in arcuate nucleus neurones: PI3K dependent actin reorganization and K-ATP channel activation' BMC Neuroscience, vol. 5, 54, pp. -.
https://doi.org/10.1186/1471-2202-5-54

Research output: Contribution To Journal



Cole, AR, Knebel, A, Morrice, NA, Robertson, LA, Irving, AJ, Connolly, CN & Sutherland, C 2004,

'GSK-3 phosphorylation of the Alzheimer epitope within collapsin response mediator proteins regulates axon elongation in primary neurons' Journal of Biological Chemistry, vol. 279, no. 48, pp. 50176-50180.
https://doi.org/10.1074/jbc.C400412200

Research output: Contribution To Journal



Finlay, D, Patel, S, Dickson, LM, Shpiro, N, Marquez, R, Rhodes, CJ & Sutherland, C 2004,

'Glycogen synthase kinase-3 regulates IGFBP-1 gene transcription through the thymine-rich insulin response element' BMC Molecular Biology, vol. 5, 15, pp. -.
https://doi.org/10.1186/1471-2199-5-15

Research output: Contribution To Journal



Grempler, R, Kienitz, A, Werner, T, Meyer, M, Barthel, A, Ailett, F, Sutherland, C, Walther, R & Schmoll, D 2004,

'Tumour necrosis factor a decreases glucose-6-phosphatase gene expression by activation of nuclear factor k B' Biochemical Journal, vol. 382, pp. 471-479.
https://doi.org/10.1042/BJ20040160

Research output: Contribution To Journal



Kinsella, JM, Laidlaw, HA, Tang, T, Harvey, J, Sutherland, C & Ashford, MLJ 2004,

'The aminoguanidine carboxylate BVT.12777 activates ATP-sensitive K+ channels in the rat insulinoma cell line, CRI-G1' BMC Clinical Pharmacology, vol. 4, no. 17.
https://doi.org/10.1186/1471-2210-4-17

Research output: Contribution To Journal



Patel, S, Lipina, C & Sutherland, C 2003,

'Different mechanisms are used by insulin to repress three genes that contain a homologous thymine-rich insulin response element' FEBS Letters, vol. 549, no. 1-3, pp. 72-76.
https://doi.org/10.1016/S0014-5793(03)00774-9

Research output: Contribution To Journal



Patel, S, Lochhead, PA, Rena, G, Fumagalli, S, Pende, M, Kozma, SC, Thomas, G & Sutherland, C 2002,

'Insulin regulation of insulin-like growth factor-binding protein-1 gene expression is dependent on the mammalian target of rapamycin, but independent of ribosomal S6 kinase activity' Journal of Biological Chemistry, vol. 277, no. 12, pp. 9889-9895.
https://doi.org/10.1074/jbc.M109870200

Research output: Contribution To Journal



Patel, S, Van-Der-Kaay, J & Sutherland, C 2002,

'Insulin regulation of hepatic insulin-like growth factor-binding protein-1 (IGFBP-1) gene expression and mammalian target of rapamycin (m TOR) signalling is impaired by the presence of hydrogen peroxide' Biochemical Journal, vol. 365, pp. 537-545.
https://doi.org/10.1042/BJ20020266

Research output: Contribution To Journal



Patel, S, Lochhead, PA, Rena, G & Sutherland, C 2001,

'Antagonistic effects of phorbol esters on insulin regulation of insulin-like growth factor-binding protein-1 (IGFBP-1) but not glucose-6-phosphatase gene expression' Biochemical Journal, vol. 359, no. 3, pp. 611-619.

Research output: Contribution To Journal



Lochhead, PA, Coghlan, M, Rice, SQJ & Sutherland, C 2001,

'Inhibition of GSK-3 selectively reduces glucose-6-phosphatase and phosphoenolpyruvate carboxykinase gene expression' Diabetes, vol. 50, no. 5, pp. 937-946.
https://doi.org/10.2337/diabetes.50.5.937

Research output: Contribution To Journal



Waltner-Law, M, Daniels, MC, Sutherland, C & Granner, DK 2000,

'NF-kappa B inhibits glucocorticoid and c AMP-mediated expression of the phosphoenolpyruvate carboxykinase gene' Journal of Biological Chemistry, vol. 275, no. 41, pp. 31847-31856.
https://doi.org/10.1074/jbc.M003656200

Research output: Contribution To Journal



Wang, J-C, Stafford, JM, Scott, DK, Sutherland, C & Granner, DK 2000,

'The molecular physiology of hepatic nuclear factor 3 in the regulation of gluconeogenesis' Journal of Biological Chemistry, vol. 275, no. 19, pp. 14717-14721.
https://doi.org/10.1074/jbc.275.19.14717

Research output: Contribution To Journal



Lochhead, PA, Salt, IP, Walker, KS, Hardie, DG & Sutherland, C 2000,

'5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase' Diabetes, vol. 49, no. 6, pp. 896-903.
https://doi.org/10.2337/diabetes.49.6.896

Research output: Contribution To Journal



Kotani, K, Ogawa, W, Hino, Y, Kitamura, T, Ueno, H, Sano, W, Sutherland, C, Granner, DK & Kasuga, M 1999,

'Dominant negative forms of Akt (protein kinase B) and atypical protein kinase Cλ do not prevent insulin inhibition of phosphoenolpyruvate carboxykinase gene transcription' Journal of Biological Chemistry, vol. 274, no. 30, pp. 21305-21312.
https://doi.org/10.1074/jbc.274.30.21305

Research output: Contribution To Journal



Sutherland, C, Waltner-Law, M, Gnudi, L, Kahn, BB & Granner, DK 1998,

'Activation of the Ras mitogen-activated protein kinase ribosomal protein kinase pathway is not required for the repression of phosphoenolpyruvate carboxykinase gene transcription by insulin' Journal of Biological Chemistry, vol. 273, no. 6, pp. 3198-3204.
https://doi.org/10.1074/jbc.273.6.3198

Research output: Contribution To Journal



Sutherland, C, Tebbey, PW & Granner, DK 1997,

'Oxidative and chemical stress mimic insulin by selectively inhibiting the expression of phosphoenolpyruvate carboxykinase in hepatoma cells' Diabetes, vol. 46, no. 1, pp. 17-22.

Research output: Contribution To Journal



Sutherland, C, O'Brien, RM, Granner, DK, Saklatvala, J, Cohen, P & White, MF 1996,

'New connections in the regulation of PEPCK gene expression by insulin [and discussion]' Philosophical Transactions of the Royal Society B - Biological Sciences, vol. 351, no. 1336, pp. 191-199.
https://doi.org/10.1098/rstb.1996.0016

Research output: Contribution To Journal



Gabbay, RA, Sutherland, C, Gnudi, L, Kahn, BB, O'Brien, RM, Granner, DK & Flier, JS 1996,

'Insulin regulation of phosphoenolpyruvate carboxykinase gene expression does not require activation of the Ras mitogen-activated protein kinase signaling pathway' Journal of Biological Chemistry, vol. 271, no. 4, pp. 1890-1897.
https://doi.org/10.1074/jbc.271.4.1890

Research output: Contribution To Journal



Osawa, H, Sutherland, C, Robey, RB, Printz, RL & Granner, DK 1996,

'Analysis of the signaling pathway involved in the regulation of hexokinase II gene transcription by insulin' Journal of Biological Chemistry, vol. 271, no. 28, pp. 16690-16694.
https://doi.org/10.1074/jbc.271.28.16690

Research output: Contribution To Journal



Sutherland, C, O'Brien, RM & Granner, DK 1995,

'Phosphatidylinositol 3-Kinase, but not p70/p85 ribosomal S6 protein kinase, is required for the regulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by insulin: dissociation of signaling pathways for insulin and phorbol ester regulation of PEPCK gene expression' Journal of Biological Chemistry, vol. 270, no. 26, pp. 15501-15506.
https://doi.org/10.1074/jbc.270.26.15501

Research output: Contribution To Journal



Sutherland, C & Cohen, P 1994,

'The α-isoform of glycogen synthase kinase-3 from rabbit skeletal muscle is inactivated by p70 S6 kinase or MAP kinase-activated protein kinase-1 in vitro' FEBS Letters, vol. 338, no. 1, pp. 37-42.
https://doi.org/10.1016/0014-5793(94)80112-6

Research output: Contribution To Journal



Sutherland, C, Leighton, IA & Cohen, P 1993,

'Inactivation of glycogen-synthase kinase-3-beta by phosphorylation: new kinase connections in insulin and growth-factor signaling' Biochemical Journal, vol. 296, no. 1, pp. 15-19.

Research output: Contribution To Journal



Sutherland, C, Leighton, IA & Cohen, P 1993,

'Inactivation of glycogen synthase kinase-3β by phosphorylation: New kinase connections in insulin and growth-factor signalling' Biochemical Journal, vol. 296, no. 1, pp. 15-19.
https://doi.org/10.1042/bj2960015

Research output: Contribution To Journal



Sutherland, C, Campbell, DG & Cohen, P 1993,

'Identification of insulin-stimulated protein kinase-1 as the rabbit equivalent of rskmo-2: identification of two threonines phosphorylated during activation by mitogen-activated protein kinase' European Journal of Biochemistry, vol. 212, no. 2, pp. 581-588.
https://doi.org/10.1111/j.1432-1033.1993.tb17696.x

Research output: Contribution To Journal



Sutherland, C, Alterio, J, Campbell, DG, Le Bourdellès, B, Mallet, J, Haavik, J & Cohen, P 1993,

'Phosphorylation and activation of human tyrosine hydroxylase in vitro by mitogen-activated protein (MAP) kinase and MAP-kinase-activated kinases 1 and 2' European Journal of Biochemistry, vol. 217, no. 2, pp. 715-722.
https://doi.org/10.1111/j.1432-1033.1993.tb18297.x

Research output: Contribution To Journal



Cohen, P, Campbell, DG, Dent, P, Gomez, N, Lavoinne, A, Nakielny, S, Stokoe, D, Sutherland, C & Traverse, S 1992,

'Dissection of the protein kinase cascades involved in insulin and nerve growth factor action' Biochemical Society Transactions, vol. 20, no. 3, pp. 671-674.
https://doi.org/10.1042/bst0200671

Research output: Contribution To Journal



Williams, RJ, Mc Carthy, AD & Sutherland, CD 1989,

'Esterification and absorption of cholesterol: in vitro and in vivo observations in the rat' Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism, vol. 1003, no. 2, pp. 213-216.
https://doi.org/10.1016/0005-2760(89)90259-2

Research output: Contribution To Journal



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Diabetes UK Professional Conference 2013

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Activity: Participation in conference

13 3 2010

Diabetes UK (External organisation)

Role: Member
Activity: Membership of external research organisation

  2010