Dr Greg Smith

Fields of research: Signal Transduction, Cell Metabolism, Biochemistry and Cell Biology

Contact Details

Phone: 029385 8075
Email: g.smith@unsw.edu.au

Tabs

Main

Current Research Areas

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.

Honours and Awards

Foundation of Science, Research and Technology Fellowship, New Zealand (2012-2014)

University role:

Senior Lecturer

Groups:

Metabolic Signalling Lab

Research

Socio-economic Objective (SEO) tags:

Diabetes

Mental Health

Teaching & Supervision

I am available to supervise:

Yes

Areas of supervision:

ILP, Honours, Masters, PhD

Supervision keywords:

diabetes

endocrinology & metabolism

cellular signalling pathways

glucose

animal models

glucagon

insulin

Publications related to this Person

Journal articles

Nemati R; Lu J; Tura A; Smith G; Murphy R, 2017, 'Acute Changes in Non-esterified Fatty Acids in Patients with Type 2 Diabetes Receiving Bariatric Surgery', Obesity Surgery, vol. 27, pp. 649 - 656, 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 Ser⁵⁵²on β-catenin in primary rat hepatocytes via PKA signalling', Biochemical Journal, vol. 473, 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, 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, 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, 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, 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, 2015, 'Akt activation increases cellular cholesterol by promoting the proteasomal degradation of Niemann-Pick C1', Biochemical Journal, vol. 471, 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, 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, pp. 88 - 96, http://dx.doi.org/10.3109/13813455.2015.1048693

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, http://dx.doi.org/10.1371/journal.pone.0096489

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; Zhang ZY; Mulvey T; Petersen N; Lach S; Xiu P; Phillips A; Han W; Wang MW; Shepherd PR, 2014, 'Clozapine directly increases insulin and glucagon secretion from islets: Implications for impairment of glucose tolerance', Schizophrenia Research, vol. 157, pp. 128 - 133, http://dx.doi.org/10.1016/j.schres.2014.05.003

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

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, 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 & 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, 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, 2013, 'Extended treatment with selective phosphatidylinositol 3-kinase and mTOR inhibitors has effects on metabolism, growth, behaviour and bone strength', FEBS Journal, vol. 280, 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 & Clinical Practice, vol. 6, pp. 54 - 54, http://dx.doi.org/10.1016/j.orcp.2012.08.110

Smith GC; Ong WK; Rewcastle GW; Kendall JD; Han W; Shepherd PR, 2012, 'Effects of acutely inhibiting PI3K isoforms and mTOR on regulation of glucose metabolism in vivo', Biochemical Journal, vol. 442, pp. 161 - 169, http://dx.doi.org/10.1042/BJ20111913

Donges CE; Burd NA; Duffield R; Smith GC; West DWD; Short MJ; Mackenzie R; Plank LD; Shepherd PR; Phillips SM, 2012, 'Concurrent resistance and aerobic exercise stimulates both myofibrillar and mitochondrial protein synthesis in sedentary middle-aged men', Journal of Applied Physiology, vol. 112, pp. 1992 - 2001, http://dx.doi.org/10.1152/japplphysiol.00166.2012

de Bock M; Derraik JGB; Brennan CM; Biggs JB; Smith GC; Cameron-Smith D; Wall CR; Cutfield WS, 2012, 'Psyllium supplementation in adolescents improves fat distribution & lipid profile: A randomized, participant-blinded, placebo-controlled, crossover trial', PLoS ONE, vol. 7, http://dx.doi.org/10.1371/journal.pone.0041735

Costa JL; Smith G; Watson M; Lin JM; Callon K; Gamble G; Cheng A; Vickers MH; Shepherd PR; Cornish J, 2011, 'The atypical anti-psychotic clozapine decreases bone mass in rats in vivo', Schizophrenia Research, vol. 126, pp. 291 - 297, http://dx.doi.org/10.1016/j.schres.2010.11.024

Smith GC; Vickers MH; Shepherd PR, 2011, 'Olanzapine effects on body composition, food preference, glucose metabolism and insulin sensitivity in the rat', Archives of Physiology and Biochemistry, vol. 117, pp. 241 - 249, http://dx.doi.org/10.3109/13813455.2011.576681

Smith GC; Konycheva G; Dziadek MA; Ravelich SR; Patel S; Reddy S; Breier BH; Vickers MH; Owens JA; Ferguson LR, 2011, 'Pre-and postnatal methyl deficiency in the rat differentially alters glucose homeostasis', Journal of Nutrigenetics and Nutrigenomics, vol. 4, pp. 175 - 191, http://dx.doi.org/10.1159/000330227

Smith GC; Vickers MH; Cognard E; Shepherd PR, 2009, 'Clozapine and quetiapine acutely reduce glucagon-like peptide-1 production and increase glucagon release in obese rats: Implications for glucose metabolism and food choice behaviour', Schizophrenia Research, vol. 115, pp. 30 - 40, http://dx.doi.org/10.1016/j.schres.2009.07.011

Smith GC; Chaussade C; Vickers M; Shepherd PR, 2008, 'Second generation antipsychotic medications induce type 2 diabete like syndrome by increasing hepatic glucose output and subsequently insulin secretion: Implications for mechanism of drug action', European Psychiatry, vol. 23, pp. S169 - S169, http://dx.doi.org/10.1016/j.eurpsy.2008.01.967

Smith GC; Chaussade C; Vickers M; Jensen J; Shepherd PR, 2008, 'Atypical antipsychotic drugs induce derangements in glucose homeostasis by acutely increasing glucagon secretion and hepatic glucose output in the rat', Diabetologia, vol. 51, pp. 2309 - 2317, http://dx.doi.org/10.1007/s00125-008-1152-3

Conference Papers

Chowdhury MKH; Morris M; Turner N; Wu L; Shepherd P; Smith G, 2017, 'Niclosamide blocks glucagon phosphorylation of serine 552 on beta-catenin leading to decrease target genes expression and improve glucose metabolism via PKA signalling pathway', in FASEB JOURNAL, FEDERATION AMER SOC EXP BIOL, Chicago, IL, presented at Annual Meeting of the American-Society-for-Pharmacology-and-Experimental-Therapeutics (ASPET) at Experimental Biology Meeting, Chicago, IL, 22 - 26 April 2017, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000405461402087&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a

Jamieson SM; Smith GC; Kolekar S; Lee W-J; Singh R; Buchanan C; Denny WA; Han W; Kendall JD; Rewcastle GW, 2011, 'Abstract B162: Inhibition of the p110 isoform of PI 3-kinase prevents PIK3CA H1047R mutant tumor growth but is associated with impaired glucose metabolism.', in Molecular Cancer Therapeutics, pp. B162 - B162, http://dx.doi.org/10.1158/1535-7163.TARG-11-B162