研究领域

Signal Transduction

How do schizophrenia drugs affect glucose metabolism? The second generation antipsychotic drugs olanzapine and clozapine are the most effect medications for treating schizophrenia. But they also induce diabetes in a large number of people taking these drugs. Our research has uncovered new explanations on how these drugs cause alterations in glucose metabolism. We are now focused on replicating our results in the clinic. Defining the role of retinol-binding protein-4 (RBP4) on glucose production and cellular signalling events in the liver. Recently, RBP4 has been linked with obesity and diabetes in people. We recently found high levels of RBP4 in obese people with diabetes but immediately after bariatric surgery the levels dropped along with blood glucose. We are very interested in studying the role of RBP4 in glucose production and cellular signalling in the liver. The role of Interleukin-6 (IL-6) in hepatic glucose production For a number of years it has been thought that IL-6 regulates hepatic glucose production in response to exercise. We have set up an isolated liver system to test the direct effect of IL-6 on hepatic glucose production with the aim of uncovering the role of IL-6 in liver metabolism.

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Nemati R; Lu J; Tura A; Smith G; Murphy R, 2016, 'Acute Changes in Non-esterified Fatty Acids in Patients with Type 2 Diabetes Receiving Bariatric Surgery', Obesity Surgery, pp. 1 - 8, http://dx.doi.org/10.1007/s11695-016-2323-9 Chowdhury MKH; Wu LE; Coleman JLJ; Smith NJ; Morris MJ; Shepherd PR; Smith GC, 2016, 'Niclosamide blocks glucagon phosphorylation of Ser552 on β-catenin in primary rat hepatocytes via PKA signalling', Biochemical Journal, vol. 473, no. 9, pp. 1247 - 1255, http://dx.doi.org/10.1042/BCJ20160121 Dent JR; Chowdhury MKH; Tchijov S; Dulson D; Smith G, 2016, 'Interleukin-6 is a negative regulator of hepatic glucose production in the isolated rat liver', Archives of Physiology and Biochemistry, vol. 122, no. 2, pp. 103 - 109, http://dx.doi.org/10.3109/13813455.2016.1146773 Mayfield K; Siskind D; Winckel K; Russell AW; Kisely S; Smith G; Hollingworth S, 2016, 'Glucagon-like peptide-1 agonists combating clozapine-associated obesity and diabetes', Journal of Psychopharmacology, vol. 30, no. 3, pp. 227 - 236, http://dx.doi.org/10.1177/0269881115625496 Thomas F; Smith GC; Lu J; Babor R; Booth M; Beban G; Chase JG; Murphy R, 2016, 'Differential Acute Impacts of Sleeve Gastrectomy, Roux-en-Y Gastric Bypass Surgery and Matched Caloric Restriction Diet on Insulin Secretion, Insulin Effectiveness and Non-Esterified Fatty Acid Levels', Obesity Surgery, vol. 26, no. 8, pp. 1924 - 1931, http://dx.doi.org/10.1007/s11695-015-2038-3 Nuora A; Chiang VSC; Milan AM; Tarvainen M; Pundir S; Quek SY; Smith GC; Markworth JF; Ahotupa M; Cameron-Smith D; Linderborg KM, 2015, 'The impact of beef steak thermal processing on lipid oxidation and postprandial inflammation related responses', Food Chemistry, vol. 184, pp. 57 - 64, http://dx.doi.org/10.1016/j.foodchem.2015.03.059 Du X; Zhang Y; Jo SR; Liu X; Qi Y; Osborne B; Byrne FL; Smith GC; Turner N; Hoehn KL; Brown AJ; Yang H, 2015, 'Akt activation increases cellular cholesterol by promoting the proteasomal degradation of Niemann-Pick C1', Biochemical Journal, vol. 471, no. 2, pp. 243 - 253, http://dx.doi.org/10.1042/BJ20150602 Murphy R; Smith G; Isaac I; Hutchinson D; Semple RK, 2015, 'Novel mutation in insulin receptor gene identified after muscle biopsy in a Niuean woman with severe insulin resistance', Diabetic Medicine, vol. 32, no. 10, pp. e24 - e28, http://dx.doi.org/10.1111/dme.12707 Chowdhury MKH; Montgomery MK; Morris MJ; Cognard E; Shepherd PR; Smith GC, 2015, 'Glucagon phosphorylates serine 552 of β-catenin leading to increased expression of cyclin D1 and c-Myc in the isolated rat liver', Archives of Physiology and Biochemistry, vol. 121, no. 3, pp. 88 - 96, http://dx.doi.org/10.3109/13813455.2015.1048693 Albert BB; Derraik JGB; Brennan CM; Biggs JB; Smith GC; Garg ML; Cameron-Smith D; Hofman PL; Cutfield WS, 2014, 'Higher omega-3 index is associated with increased insulin sensitivity and more favourable metabolic profile in middle-aged overweight men', Scientific Reports, vol. 4, http://dx.doi.org/10.1038/srep06697 Smith GC; McEwen H; Steinberg JD; Shepherd PR, 2014, 'The activation of the Akt/PKB signalling pathway in the brains of clozapine-exposed rats is linked to hyperinsulinemia and not a direct drug effect', Psychopharmacology, vol. 231, no. 23, pp. 4553 - 4560, http://dx.doi.org/10.1007/s00213-014-3608-0 Smith GC; McEwen H; Steinberg JD; Shepherd PR, 2014, 'The activation of the Akt/PKB signalling pathway in the brains of clozapine-exposed rats is linked to hyperinsulinemia and not a direct drug effect', Psychopharmacology, http://dx.doi.org/10.1007/s00213-014-3608-0 Smith GC; Mulvey T; Lach S; Shepherd PR; Zhang ZY; Wang M-W; Xiu P; Petersen N; Han W; Phillips A, 2014, 'Clozapine directly increases insulin and glucagon secretion from islets: Implications for impairment of glucose tolerance', Schizophrenia Research, http://dx.doi.org/10.1016/j.schres.2014.05.003 Jüllig M; Yip S; Xu A; Smith G; Middleditch M; Booth M; Babor R; Beban G; Murphy R, 2014, 'Lower fetuin-A, retinol binding protein 4 and several metabolites after gastric bypass compared to sleeve gastrectomy in patients with type 2 diabetes.', PLoS One, vol. 9, no. 5, pp. e96489, http://dx.doi.org/10.1371/journal.pone.0096489 Donges CE; Duffield R; Smith GC; Short MJ; Edge JA, 2014, 'Cytokine mRNA expression responses to resistance, aerobic, and concurrent exercise in sedentary middle-aged men', Applied Physiology, Nutrition and Metabolism, vol. 39, no. 2, pp. 130 - 137, http://dx.doi.org/10.1139/apnm-2013-0076 Smith G, 2013, 'How do antipsychotic drugs cause diabetes and obesity?', Obesity Research and Clinical Practice, vol. 7, pp. e41 - e41, http://dx.doi.org/10.1016/j.orcp.2013.12.579 Yip S; Murphy R; Signal M; Chase JG; Smith G; Beban G; Booth M; Babor R, 2013, 'Lower Glycemic Fluctuations Early After Bariatric Surgery Partially Explained by Caloric Restriction', Obesity Surgery, pp. 1 - 9, http://dx.doi.org/10.1007/s11695-013-1043-7 Donges CE; Duffield R; Guelfi KJ; Smith GC; Adams DR; Edge JA, 2013, 'Comparative effects of single-mode vs. duration-matched concurrent exercise training on body composition, low-grade inflammation, and glucose regulation in sedentary, overweight, middle-aged men', Applied Physiology, Nutrition and Metabolism, vol. 38, no. 7, pp. 779 - 788, http://dx.doi.org/10.1139/apnm-2012-0443 Smith GC; Ong WK; Costa JL; Watson M; Cornish J; Grey A; Gamble GD; Dickinson M; Leung S; Rewcastle GW; Han W; Shepherd PR, 2013, 'Extended treatment with selective phosphatidylinositol 3-kinase and mTOR inhibitors has effects on metabolism, growth, behaviour and bone strength', The Federation of European Biochemical Societies (FEBS) Journal, vol. 280, no. 21, pp. 5337 - 5349, http://dx.doi.org/10.1111/febs.12428 de Bock M; Derraik J; Brennan C; Biggs J; Smith G; Cameron-Smith D; Wall C; Cutfield W, 2012, 'Psyllium supplementation improves parameters of the metabolic syndrome: A randomized, participant-blinded, placebo controlled, crossover trial', Obesity Research and Clinical Practice, vol. 6, pp. 54 - 54, http://dx.doi.org/10.1016/j.orcp.2012.08.110