Luke Norton, Ph.D.
Department of Medicine
I am interested in the discovery of novel molecular, metabolic and physiologic pathways in liver that contribute to the pathophysiology of type 2 diabetes and associated comorbidities such as obesity and non-alcoholic fatty liver disease (NAFLD). Currently my laboratory is interrogating the role that mitochondria play in hepatic insulin resistance, and in how hepatocyte metabolic heterogeneity in liver regulates pathways of lipid metabolism, inflammation and fibrosis in NAFLD and NASH.
- 2007 - PhD - Biomedical Science (NA) - University of Nottingham
- 2003 - BS - Human Physiology (First class honours) - University of Hertfordshire
- 1/2014 - Assistant Professor/Research - University of Texas Health Science Center at San Antonio, Medicine
- 4/2010 - Instructor and Other - University of Texas Health Science Center San Antonio (UTHSCSA), Medicine, San Antonio
Instruction & Training
- 5/2013 - Present, Ph.D. Dissertations Directed, UTHSCSA
- 5/2013 - Present, Membership on Supervising Committee, UTHSCSA
Research & Grants
Funding Agency NIH Title The role of glucose mediated glucose uptake in the pathogenesis of IFG and IGT (NIH R01DK09755401) Status Active Period 9/2012 - 9/2017 Role Co-Investigator Grant Detail Funding Agency NIH/NIA Title K01 Career Development Award Status Active Period 5/2014 - 5/2017 Role Principal Investigator Grant Detail Single-nucleotide polymorphisms (SNP) within the transcription factor 7-like 2 (TCF7L2) gene have been consistently associated with an elevated risk for type 2 diabetes (T2DM) in multiple populations throughout the world, but the mechanisms by which TCF7L2 affects the pathways important for the development of T2DM are still poorly understood. Addressing this question is of major importance, primarily because functional investigations into T2DM candidate genes will reveal novel molecular pathways that affect important physiological processes that are highly disturbed in T2DM. In several human studies, carriers of the T-allele for the "at-risk" SNP (rs7903146) have impaired hepatic glucose production (HGP) and hepatic insulin sensitivity. Preliminary findings from the laboratory of Dr Norton demonstrating that silencing of TCF7L2 markedly up- regulates HGP in vitro, strongly support a role for TCF7L2 in the pathways of HGP. The aim of this proposal is to establish the functional role of the T2DM candidate gene TCF7L2 in HGP in vivo, and to investigate the molecular mechanisms by which TCF7L2 affects the pathways of glucose metabolism in the liver. A combination of integrative physiology and genomics approaches will be used to address the central hypothesis that TCF7L2 is a major regulator of HGP in vivo and that transcriptional control of key metabolic genes by TCF7L2 in the liver is the underlying mechanism of this regulation. The major training component of this proposal is the acquisition, refinement and application of new skills, with focus on two areas: (i) integrated physiology, and (ii) functional genomics and bioinformatics. These thematic areas were selected because at the present time knowledge about these areas is extremely valuable to conduct cutting-edge diabetes research, and these areas are cohesive and highly integrated with the scientific goals of this project. In addition, the scientific objectives of this proposal will be coupled with an intensive c
Funding Agency Metabolic Solutions Devlopment Agency Title Efficacy and mechanism of action of anti-diabetic drug MSDC-0602 Status Active Period 2/2013 - Present Role Co-Investigator Grant Detail Funding Agency Title Sodium Coupled Glucose Transporter (SGLT) Expression in the Human Diabetic Kidney Status Active Period 3/2010 - Present Role Co-Principal Investigator Grant Detail
Chokkalingam K, Jewell K, Norton L, Littlewood J, van Loon LJ, Mansell P, Macdonald IA, Tsintzas K. High-fat/low-carbohydrate diet reduces insulin-stimulated carbohydrate oxidation but stimulates nonoxidative glucose disposal in humans: An important role for skeletal muscle pyruvate dehydrogenase kinase 4. J Clin Endocrinol Metab. 2007 Jan;92(1):284-92. doi: 10.1210/jc.2006-1592. Epub 2006 Oct 24. PubMed PMID: 17062764.
Norton L, Parr T, Bardsley RG, Ye H, Tsintzas K. Characterization of GLUT4 and calpain expression in healthy human skeletal muscle during fasting and refeeding. Acta Physiol (Oxf). 2007 Mar;189(3):233-40. doi: 10.1111/j.1748-1716.2006.01639.x. PubMed PMID: 17305703.
Chokkalingam K, Tsintzas K, Norton L, Jewell K, Macdonald IA, Mansell PI. Exercise under hyperinsulinaemic conditions increases whole-body glucose disposal without affecting muscle glycogen utilisation in type 1 diabetes. Diabetologia. 2007 Feb;50(2):414-21. doi: 10.1007/s00125-006-0520-0. Epub 2006 Nov 21. PubMed PMID: 17119916.
Pelsers MM, Tsintzas K, Boon H, Jewell K, Norton L, Luiken JJ, Glatz JF, van Loon LJ. Skeletal muscle fatty acid transporter protein expression in type 2 diabetes patients compared with overweight, sedentary men and age-matched, endurance-trained cyclists. Acta Physiol (Oxf). 2007 Jul;190(3):209-19. doi: 10.1111/j.1748-1716.2007.01698.x. Epub 2007 Mar 30. PubMed PMID: 17394567.
Tsintzas K, Chokkalingam K, Jewell K, Norton L, Macdonald IA, Constantin-Teodosiu D. Elevated free fatty acids attenuate the insulin-induced suppression of PDK4 gene expression in human skeletal muscle: potential role of intramuscular long-chain acyl-coenzyme A. J Clin Endocrinol Metab. 2007 Oct;92(10):3967-72. doi: 10.1210/jc.2007-1104. Epub 2007 Jul 24. PubMed PMID: 17652214.
Boonsong T, Norton L, Chokkalingam K, Jewell K, Macdonald I, Bennett A, Tsintzas K. Effect of exercise and insulin on SREBP-1c expression in human skeletal muscle: potential roles for the ERK1/2 and Akt signalling pathways. Biochem Soc Trans. 2007 Nov;35(Pt 5):1310-1. doi: 10.1042/BST0351310. PubMed PMID: 17956338.
Norton L, Parr T, Chokkalingam K, Bardsley RG, Ye H, Bell GI, Pelsers MM, van Loon LJ, Tsintzas K. Calpain-10 gene and protein expression in human skeletal muscle: effect of acute lipid-induced insulin resistance and type 2 diabetes. J Clin Endocrinol Metab. 2008 Mar;93(3):992-8. doi: 10.1210/jc.2007-1981. Epub 2007 Dec 18. PubMed PMID: 18089694; PubMed Central PMCID: PMC2729205.
Chokkalingam K, Tsintzas K, Snaar JEM, Norton L, Solanky B, Leverton E, Morris P, Mansell P, Macdonald IA. Hyperinsulinaemia during exercise does not suppress hepatic glycogen concentrations in patients with type 1 diabetes: a magnetic resonance spectroscopy study. Diabetologia. 2007 Sep;50(9):1921-1929. doi: 10.1007/s00125-007-0747-4. Epub 2007 Jul 18. PubMed PMID: 17639304.