1 / 12

Diabetes & Metabolic Health Research Group Centre for Biomedical Science,

Diabetes & Metabolic Health Research Group Centre for Biomedical Science, Cardiff School of Health Sciences. Diabetes & Metabolic Health Research Group. Inflammatory/cell-signaling aspects of diabetes-associated cardiovascular disease (CVD).

alder
Télécharger la présentation

Diabetes & Metabolic Health Research Group Centre for Biomedical Science,

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Diabetes & Metabolic Health Research Group Centre for Biomedical Science, Cardiff School of Health Sciences

  2. Diabetes & Metabolic Health Research Group. • Inflammatory/cell-signaling aspects of diabetes-associated cardiovascular disease (CVD). • The effect of PPAR ligands in modulating inflammatory processes in complications of Type 2 Diabetes (T2D). • The effect of exercise, and of dietary lipids, on the prevention and progression of T2D, obesity and CVD.

  3. What are PPAR Ligands? • Natural Ligands • Dietary Ligands (eg. conjugated linoleic acid(CLA)) • Prostaglandin metabolites. (e.g. 15-deoxy-delta 12,14-prostaglandin J2 (15d-PGJ2 ) • oxidised LDL as a source of HODEs (hydroxy-octadecadienoic acid) • Synthetic Ligands. • Thiazolidinediones (eg. Rosiglitazone) Rosiglitazone

  4. The role of PPARligands in T2D. • On binding of a ligand, PPAR acts as a transcription factor, regulating expression of specific target genes(eg. CD36, LPL, LXRa, etc) . • PPAR exerts beneficial effects in T2D by regulating the expression of genes involved in:- • glucose & lipid metabolism; cell differentiation. • inflammatory processes relevant to the progression of Type 2 Diabetes & its complications. • PPAR ligands also exert PPAR -independent effects (eg. the Unfolded Protein Response) that are relevant to T2D.

  5. Diabetes & Metabolic Health Research Group - Principal Investigators • Richard Webb • (Head of group 2009-2010; • Intracellular Signalling) • Intracellular signalling events triggered by exercise in normal subjects. • The role of the Unfolded Protein Response (UPR) and ER stress in diabetes and obesity. • Keith Morris • (Inflammatory Biology; Biostatistics) • Effect of endogenous dietary and other ligands of PPARs on inflammatory processes associated with diabetes and atherosclerosis. • The effects of low intensity exercise on cardiovascular risk markers and lipid metabolism • Andrew Thomas • (Molecular Biology) • Role of PPAR in diabetes and the process of atherosclerosis • Exercise-induced modulation of PPAR activity in normal and diabetic subjects • Role of endothelial and macrophage AGE-RAGE interaction in diabetes and atherosclerosis. • Rachel Adams • (Rheology) • Effect of air borne particles on cardiovascular risk markers • Factors affecting blood flow and blood cell deformability in diabetes • Barry McDonnell • (Vascular Biology; Early career researcher) • Arterial stiffness

  6. Group Strategy - Research Areas: • Main theme: Advantageous effects of PPAR activation in T2D/obesity/CVD, & elucidation of the mechanisms by which they occur. • Interventions leading to PPAR activation (exercise; dietary supplementatn), as investigated in terms of the following: • Generation of PPAR & other ligands (eg. oxLDL? HODEs? Oxysterols?) • Triggering of signalling pathways that lead to PPAR activation (eg. AMPK/sirtuin/PGC1α axis) • Anti-Atherogenic/Anti-Inflammatory processes linked to PPAR activation (eg. M1/M2 subtypes; RAGE splicing; arterial stiffness; etc) • Subsidiary Themes: • Strategies for alleviation of ER stress, as seen in macrophage lipotoxicity in obesity/T2D. • Cytoskeletal remodelling and leukocyte rigidity, leading to prevention of microvascular diabetic complications

  7. Ongoing projects:- • Low-intensity exercise modulates PPAR-regulated expression of target genes responsible for reverse cholesterol transport, in previously sedentary adults. • Nia Davies (PhD) [PI: RW] • The Effect of Dietary/Natural PPAR Ligands and other Lipids On Cell Signalling Processes Relevant To The Development Of T2D And Its Complications. • Lowri Mainwaring (PhD), Hemanth Bolusani (MD), Khalid Al-Murraimi (PhD), Gertrude Yakeu (MPhil) [PI: KM in all cases] • The Induction of ER Stress Responses by Cholesterol, Rosiglitazone and various natural PPARgamma Ligands. • Jo Caddy (PhD), Suleiman Isa (PhD) [PI: RW in all cases] • The Effects of lifestyle, disease and the environment on blood flow. • Michael Melhuish (PhD (in collab with Prince Charles Hospital, Merthyr)), Halima Al-Bulushi (MPhil) [PI: RA in all cases]

  8. Pending Funding Applications • EASD Postdoctoral Scientist (TBA). • Submitted Nov 2009; Outcome expected March 2010 • WORD Early Career Researcher (Barry McDonnell). The effects of exercise on serum lipid profiles, arterial stiffness and PPAR-activated gene expression in patients with Metabolic Syndrome. • Submitted May 2009; Outcome expected early 2010 • WORD PhD studentship (Jose Ruffino). • Submitted July 2009; Outcome expected Jan 2010 • Diabetes UK Project Grant (in preparation). - Community walking & PPAR-activated gene expression in patients with Diabetes (with Swansea Uni/Cardiff Uni).

  9. Current students:- • 7 PhD/MPhil students - Joanne Caddy, Suleiman Isa, Nia Davies, Khalid Al-Muharrami, Lowri Mainwaring, Gertrude Yakeu, Halima Al-Bulushi. • 1 MD student – Hemanth Bolusani (UHW) • 1 External PhD student – Michael Melhuish (Prince Charles Hospital, Merthyr)

  10. Recent Funding Awards • WORD Health PhD studentship (£60K; awarded April 2009) The mechanisms underpinning potentially anti-atherogenic PPARγ-agonist generation during low-intensity exercise: a molecular rationale for prescribing exercise to patients? • HEFCW Postgraduate PhD Scholarship (£110K; awarded Oct 2007) The Role of CLA in PPAR-activated gene expression, with relation to low-intensity exercise, markers of inflammation and cardiovascular disease.

  11. Collaborators:- • Welsh Diabetes Research Network • Welsh Cardiovascular Interdisciplinary Research Group • Dr M Evans (Llandough Hospital) • Dr A Roberts, Dr M Ludgate (School of Medicine, Cardiff University) • Dr D Lang, Dr P James (Wales Heart Research Institute, Cardiff University) • Prof S Jackson (UWE) • Dr R Bracken (Swansea University) • Dr K Backx, Dr M Hughes (UWIC School of Sport) • Dr John Geen (Prince Charles Hospital, Merthyr)

  12. Recent Publications. • Isa, S.A., Mainwaring, L.S., Webb. R. and Thomas, A.W. (2009): “The Non-Genomic Effects of High Doses of Rosiglitazone on Cell Growth and Apoptosis in Cultured Monocytic Cells”Bayero Journal of Pure and Applied Sciences 2(2): pp.1-8. • Butcher et al (2008) Low Intensity Exercise Exerts Beneficial Effects on Plasma Lipids via PPAR. J. Med Sci Sports Ex. 40 (7): 1–7 • Caddy et al (2008) Rosiglitazone Transiently Disturbs Calcium Homeostasis in Monocytic Cells. BiochemBiophys Res Comm. 366(1):149-55 • Atkin et al (2008) Rosiglitazone-Induced SERCA2b Inhibition: Implications for MonocyteCytoskeletalRemodeling and Diabetic Microangiopathy. Bioscience Horizons1:1-8. • Khanolkar et al (2008) Rosiglitazone produces a greater reduction in circulating platelet activity compared with gliclazide in patients with type 2 diabetes mellitus-An effect probably mediated by direct platelet PPARgamma activation. Atherosclerosis 197(2):718-24 • Moir, H., et al (2008) AMPK Inactivation in Mononuclear Cells: A Potential Intracellular Mechanism For Exercise-Induced Immunosuppression. Applied Physiology, Nutrition and Metabolism33:. 75-85

More Related