A/Prof Carsten Schmitz-Peiffer

Lab Head - Insulin Signalling

Senior Research Fellow

Conjoint/Adjunct Role(s)

Associate Professor, St Vincent's Clinical School, Faculty of Medicine, UNSW Australia

Carsten Schmitz-Peiffer undertook his PhD with Professor Dick Denton at Bristol University (UK), where he investigated insulin signal transduction and the regulation of fat cell metabolism. He then joined the Garvan Institute to investigate mechanisms by which lipid oversupply could interfere with normal insulin action. His research showed an association between protein kinase C activation and lipid-induced insulin resistance in skeletal muscle. Subsequently he demonstrated a causative link between intracellular accumulation of the lipid intermediate ceramide and the inhibition of insulin action caused by the saturated fatty acid palmitate. It is thus clear that different fatty acids act through different mechanisms to reduce insulin sensitivity.

In addition, the study of mice deficient in specific protein kinase C isoforms has indicated that these enzymes play multiple and unexpected roles in the control of glucose and lipid metabolism, beyond the mere inhibition of proximal insulin signalling as currently widely assumed, and the understanding of the diverse mechanisms involved is a major focus of his work. His research group employs animal models of insulin resistance in combination with transgenic mice, as well as proteomic and lipidomic approaches at both the in vivo and in vitro level, to generate new insights into the molecular mechanisms involved in the defective insulin action seen in obesity and Type 2 diabetes.

Carsten Schmitz-Peiffer has been a member of the program organising committee for the Australian Diabetes Society annual scientific meeting (2009-2011), as well as a member of NHMRC Endocrinology and Biochemistry grant review panels (2006, 2011-2012). Within the Garvan, he has chaired the Faculty (2010), the Common Users of Building and Equipment (CUBE) Committee (1996-2010) and the Seminar Committee (2007-2012), and currently chairs the Facilities and Equipment Committee.

Research Interests

To define the interactions between protein kinase C isoforms, lipid metabolism and insulin action
To identify the enzymes and intermediates of sphingolipid metabolism which affect insulin sensitivity
To examine the effectiveness of targeting key molecules for the treatment of diabetes

Awards and Honours

2006 - Senior Research Fellowship, Garvan Institute
1987 - Smith Kline & French/Bristol University CASE Award, UK
1986 - Exibitioner, Natural Sciences, Cambridge University, UK

Education

1990 - PhD Biochemistry, University of Bristol - UK
1987 - BA (Hons) Natural Sciences, Cambridge University - UK

Patents

US8598146 B2

Methods for identifying modulators of protein kinase C-epsilon (PKCε) and method of treatment of aberrant glucose metabolism associated therewith

Selected Publications

B. Hayward,  J. C. Molero, K. Windmill, A. Sanigorski, J. Weir, N. L. McRae, K. Aston-Mourney, B. Osborne, B. Liao, K. R. Walder, P.J. Meikle, N. Konstantopoulos, C. Schmitz-Peiffer.  Pathways of Acetyl-CoA Metabolism Involved in the Reversal of Palmitate-Induced Glucose Production by Metformin and Salicylate. (2016)  Experimental and Clinical Endocrinology & Diabetes. In Press.

B. M. Liao, S. A. McManus, W. E. Hughes,  C. Schmitz-Peiffer.  Flavin-Containing Monooxygenase 3 Reduces Endoplasmic Reticulum Stress in Lipid-Treated Hepatocytes. (2016)  Mol Endocrinol. 30(4):417-28.

Liao BM, Raddatz K, Zhong L, Parker BL, Raftery MJ, Schmitz-Peiffer C. Proteomic Analysis of Livers from Fat-fed Mice Deficient in Either PKC delta or PKC epsilon Identifies Htatip2 as a Regulator of Lipid Metabolism.  (2014) Proteomics 14:2578-87

Frangioudakis G, Diakanastasis B, Liao M, Saville J, Mitchell T, Schmitz-Peiffer C. Ceramide accumulation in L6 skeletal muscle cells due to increased activity of ceramide synthase isoforms has opposing effects on insulin action to that caused by palmitate treatment. (2013) Diabetologia 56:2697-701

Schmitz-Peiffer C. The tail wagging the dog - regulation of lipid metabolism by protein kinase C. (2013) FEBS J 280:5371-83

Pedersen DJ, Diakanastasis B, Stöckli J, Schmitz-Peiffer C. Protein Kinase C epsilon Modulates Insulin Receptor Localization and Trafficking in Mouse Embryonic Fibroblasts. (2013) PLOS One 8:e58046.

Raddatz K, Frangioudakis G, Diakanastasis B, Liao BM, Leitges M, Schmitz-Peiffer C. Deletion of protein kinase Cε in mice has limited effects on liver metabolite levels but alters fasting ketogenesis and gluconeogenesis. (2012) Diabetologia 55:2789-93

Raddatz K, Turner N, Fangioudakis G, Liao M, Cantley J, Wilks D, Preston E, Hegarty BD, Leitges M, Raftery M, Biden TJ and Schmitz-Peiffer C. Time-dependent effects of PKCε deletion on glucose homeostasis and hepatic lipid metabolism in short term and chronic models of dietary lipid oversupply. (2011) Diabetologia 54:1447-1456

Schmitz-Peiffer C. Invited Commentary: Targeting de novo ceramide synthesis to improve insulin resistance. (2010) Diabetes 59: 2351-2353

Frangioudakis G, Garrard J, Raddatz K, Nadler JL, Mitchell TW, Schmitz-Peiffer C. Saturated and n-6 polyunsaturated fat diets each induce ceramide accumulation in mouse skeletal muscle: reversal and improvement of glucose tolerance by lipid metabolism inhibitors. (2010) Endocrinology 151:4187-96

Frangioudakis G, Burchfield JG, Narasimhan S, Cooney GJ, Leitges M, Biden TJ, Schmitz-Peiffer C. Diverse roles for protein kinase C delta and protein kinase C epsilon in the generation of high-fat-diet-induced glucose intolerance in mice: regulation of lipogenesis by protein kinase C delta. (2009) Diabetologia 52:2616-2620

Schmitz-Peiffer C, Biden TJ. (2008) Perspectives in Diabetes: Protein kinase C function in muscle, liver, and beta-cells and its therapeutic implications for type 2 diabetes. Diabetes 57: 1774-1783

Schmitz-Peiffer C, Laybutt DR, Burchfield JG, Gurisik E, Narasimhan S, Mitchell CJ, Pedersen DJ, Braun U, Cooney GJ, Leitges M, Biden TJ. (2007) Inhibition of PKC epsilon Improves Glucose-Stimulated Insulin Secretion and Reduces Insulin Clearance. Cell Metab. 6:320-328

Cazzolli R, Mitchell TW, Burchfield J, Pedersen, D.J., Turner, N., Biden TJ, Schmitz-Peiffer C. (2007) Dilinoleoyl-phosphatidic acid mediates reduced IRS-1 tyrosine phosphorylation in rat skeletal muscle cells and mouse muscle. Diabetologia 50:1732-42

Burchfield JG, Lennard AJ, Narasimhan S, Hughes WE, Wasinger VC, Corthals GL, Okuda T, Kondoh H, Biden TJ, and Schmitz-Peiffer C. (2004) Akt mediates insulin-stimulated phosphorylation of Ndrg2 - evidence for crosstalk with protein kinase C theta. J. Biol. Chem. 279: 18623-18632

Cazzolli R, Carpenter L, Biden TJ, Schmitz-Peiffer C. (2001) A Role for Protein Phosphatase 2A, but not atypical Protein Kinase C zeta, in The Inhibition of Protein Kinase B/Akt and Glycogen Synthesis by Palmitate. Diabetes 50: 2210-2218

Schmitz-Peiffer C, Craig DL, Biden TJ (1999) Ceramide generation is sufficient to account for the inhibition of insulin-stimulated PKB pathway in C2C12 cells pretreated with palmitate. J. Biol. Chem. 274: 24202-24210

Schmitz-Peiffer C, Browne CL, Oakes ND, Watkinson A, Chisholm DJ, Kraegen EW, Biden TJ (1997) Alterations in the expression and cellular localization of Protein Kinase C isozymes epsilon and theta are associated with insulin resistance in skeletal muscle of the high-fat-fed rat. Diabetes 46: 169-178

A/Prof Carsten Schmitz-Peiffer