Greg Smith

Senior Lecturer

 

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)

 

publications

Journal articles
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Prodhan UK; Pundir S; Chiang VSC; Milan AM; Barnett MPG; Smith GC; Markworth JF; Knowles SO; Cameron-smith D, 2020, 'Comparable postprandial amino acid and gastrointestinal hormone responses to beef steak cooked using different methods: A randomised crossover trial', Nutrients, vol. 12, http://dx.doi.org/10.3390/nu12020380
2020
Metcalfe LK; Krishnan M; Turner N; Yaghootkar H; Merry TL; Dewes O; Hindmarsh JH; De Zoysa J; Dalbeth N; Stamp LK; Merriman TR; Smith G; Shepherd P; Murphy R, 2020, 'The Māori and Pacific specific CREBRF variant and adult height', International Journal of Obesity, vol. 44, pp. 748 - 752, http://dx.doi.org/10.1038/s41366-019-0437-6
2020
Metcalfe LK; Smith GC; Turner N, 2019, 'Defining lipid mediators of insulin resistance: controversies and challenges', JOURNAL OF MOLECULAR ENDOCRINOLOGY, vol. 62, pp. R65 - R82, http://dx.doi.org/10.1530/JME-18-0023
2019
Abdel Shaheed C; Carland JE; Graham GG; Stocker SL; Smith G; Hicks M; Williams KM; Furlong T; Macdonald P; Greenfield JR; Smith FC; Chowdhury G; Day RO, 2019, 'Is the use of metformin in patients undergoing dialysis hazardous for life? A systematic review of the safety of metformin in patients undergoing dialysis', British Journal of Clinical Pharmacology, vol. 85, pp. 2772 - 2783, http://dx.doi.org/10.1111/bcp.14107
2019
Smith GC, 2017, 'FOX01 Is the Headline Akt Regulating Hepatic Glucose Metabolism', Endocrinology, vol. 158, pp. 2436 - 2438, http://dx.doi.org/10.1210/en.2017-00525
2017
Rewcastle GW; Kolekar S; Buchanan CM; Gamage SA; Giddens AC; Tsang KY; Kendall JD; Singh R; Lee WJ; Smith GC; Han W; Matthews DJ; Denny WA; Shepherd PR; Jamieson SMF, 2017, 'Biological characterization of SN32976, a selective inhibitor of PI3κ and mTOR with preferential activity to PI3κα, in comparison to established pan PI3κ inhibitors', Oncotarget, vol. 8, pp. 47725 - 47740, http://dx.doi.org/10.18632/oncotarget.17730
2017
Chowdhury MKH; Turner N; Bentley NL; Das A; Wu LE; Richani D; Bustamante S; Gilchrist RB; Morris MJ; Shepherd PR; Smith GC, 2017, 'Niclosamide reduces glucagon sensitivity via hepatic PKA inhibition in obese mice: Implications for glucose metabolism improvements in type 2 diabetes', Scientific Reports, vol. 7, http://dx.doi.org/10.1038/srep40159
2017
Larsen PS; Donges CE; Guelfi KJ; Smith GC; Adams DR; Duffield R, 2017, 'Effects of aerobic, strength or combined exercise on perceived appetite and appetite-related hormones in inactive middle-aged men', International Journal of Sport Nutrition and Exercise Metabolism, vol. 27, pp. 389 - 398, http://dx.doi.org/10.1123/ijsnem.2017-0144
2017
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
2016
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 Among Patients with Type 2 Diabetes', Obesity Surgery, vol. 26, pp. 1924 - 1931, http://dx.doi.org/10.1007/s11695-015-2038-3
2016
Smith GC, 2016, '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
2016
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, pp. 1247 - 1255, http://dx.doi.org/10.1042/BCJ20160121
2016
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
2016
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, pp. 243 - 253, http://dx.doi.org/10.1042/BJ20150602
2015
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
2015
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
2015
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
2015
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
2014
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
2014
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
2014
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
2014
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
2014
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', FEBS Journal, vol. 280, pp. 5337 - 5349, http://dx.doi.org/10.1111/febs.12428
2013
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
2013
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
2013
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
2013
Donges CE; Burd NA; Duffield R; Smith GC; West DWD; Short MJ; Mackenzie R; Plank LD; Shepherd PR; Phillips SM; Edge JA, 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
2012
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
2012
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
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
2012
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
2011
Costa JL; Smith G; Watson M; Lin JM; Callon K; Gamble G; Cheng A; Vickers MH; Shepherd PR; Cornish J; Grey A, 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
2011
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
2011
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
2009
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
2008
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
2008
Book Chapters
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Osborne B; Brandon A; Smith GC; Turner N, 2019, 'Impact of Lifestyle and Clinical Interventions on Mitochondrial Function in Obesity and Type 2 Diabetes', in Morio B; Pénicaud L; Rigoulet M (ed.), Mitochondria in Obesity and Type 2 Diabetes, Elsevier, pp. 367 - 397, http://dx.doi.org/10.1016/C2016-0-01694-7
2019
Conference Papers
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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 April 2017 - 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=891bb5ab6ba270e68a29b250adbe88d1
2017
Smith GP; Mack M, 2014, 'Practical Considerations for Interpreting Flood Hazard', in Hydrology and Water Resources Symposium 2014, Engineers Australia, Perth, pp. 293 - 301, presented at 35th Hydrology and Water Resources Symposium, Perth, 24 February 2014 - 27 February 2014, http://search.informit.com.au/documentSummary;dn=389233953218405;res=IELENG
2014
Jamieson SM; Smith GC; Kolekar S; Lee W-J; Singh R; Buchanan C; Denny WA; Han W; Kendall JD; Rewcastle GW; Shepherd PR, 2011, 'Abstract B162: Inhibition of the p110αisoform of PI 3-kinase prevents PIK3CA H1047R mutant tumor growth but is associated with impaired glucose metabolism.', in mTOR / PI3-Kinase, American Association for Cancer Research, pp. B162 - B162, presented at Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA, http://dx.doi.org/10.1158/1535-7163.targ-11-b162
2011
Rahman P; Sharma A; Smith G, 2011, 'Estimating design floods for gauged urban catchments under climate change conditions case study: Cooks river, Sydney', in 34th IAHR Congress 2011 - Balance and Uncertainty: Water in a Changing World, Incorporating the 33rd Hydrology and Water Resources Symposium and the 10th Conference on Hydraulics in Water Engineering, pp. 356 - 363
2011
Shand TD; Smith G; Cox RJ; Blacka MJ, 2011, 'Development of appropriate criteria for the safety and stability of persons and vehicles in floods', in Proceedings of Hydrology and water resources, 34th IAHR World Congress, Engineers Australia, Canberra, Australia, presented at Hydrology and Water resources, 34th IAHR World Congress, Brisbane, -
2011