Project: Research council

Project Details


The health problem of type 2 diabetes is now huge with approximately 3% of the UK population (1.4 million people) suffering from the disease. This was once considered an adult onset disease but now teenagers are developing the disease. Sugars are abundant components of diet but their abnormal disposal is associated with type 2 diabetes. Improved understanding of glucose disposal by key body tissues is therefore needed. Diabetes is one of the major contributors to death from coronary heart disease. The uptake of sugars in heart is insulin stimulated but this process can be inhibited if the interior of the heart cells becomes too acidic. We plan to study the mechanism of heart cell pH maintenance and investigate the means by which this is linked to impaired glucose uptake and utilisation. Improved understanding will aid in the development of heart disease therapies. The increasing prevalence of type 2 diabetes is thought to be in part related to poor diets, and in part due to lack of exercise. We plan to study these two inter-related problems by focussing part of our programme on the processes in heart and skeletal muscle that govern the exposure of glucose uptake protein to the cell surface. This exposure can be driven by both insulin and by changes in the cell energy level resulting from exercise. We plan to utilise newly developed tools and reagents to study how the latter pathway can lead to alleviation of the poor insulin-stimulated glucose disposal found in type 2 diabetic persons. Integrating these related aspects of our investigation in the key tissues of fat, heart and muscle should add to the understanding of the delicate balance between our dietary sugar needs and excesses and this should lead to improved therapies that rebalance body chemistry.
Effective start/end date1/10/0328/02/09


  • MRC

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  • Research Output

    Highly potent and isoform-selective dual-site-binding tankyrase/Wnt signaling inhibitors that increase cellular glucose uptake and have anti-proliferative activity

    Nathubhai, A., Haikarainen, T., Koivunen, J., Murthy, S., Koumanov, F., Lloyd, M., Holman, G., Pihlajaniemi, T., Tosh, D., Lehtio, L. & Threadgill, M., 26 Jan 2017, In : Journal of Medicinal Chemistry. 60, 2, p. 814-820 7 p.

    Research output: Contribution to journalArticle

    Open Access
  • 22 Citations (Scopus)
    118 Downloads (Pure)

    Rab28 is a TBC1D1/TBC1D4 substrate involved in GLUT4 trafficking

    Zhou, Z., Menzel, F., Benninghoff, T., Chadt, A., Du, C., Holman, G. D. & Al-Hasani, H., 1 Jan 2017, In : FEBS Letters. 591, 1, p. 88-96 9 p.

    Research output: Contribution to journalLetter

  • 9 Citations (Scopus)

    Deletion of Both Rab-GTPase–Activating Proteins TBC1D1 and TBC1D4 in Mice Eliminates Insulin- and AICAR-Stimulated Glucose Transport

    Chadt, A., Immisch, A., De Wendt, C., Springer, C., Zhou, Z., Stermann, T., Holman, G. D., Loffing-cueni, D., Loffing, J., Joost, H. & Al-hasani, H., Mar 2015, In : Diabetes. 64, 3, p. 746-759 14 p.

    Research output: Contribution to journalArticle

  • 38 Citations (Scopus)