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REGULATION OF GLUCOSE-STIMULATED SECRETORY VESICLE MOBILISATION IN PANCREATIC BETA-CELLS

Objective

During meals our bodies break food down into glucose which then moves from the bloodstream into cells to be utilised. This process requires insulin production by the pancreatic beta-cells. Impaired function of these cells leads to inadequate insulin output and elevated blood glucose level. The failure of beta-cells is the main reason for the development of diabetes which affects 22.5 million people in the European Region. We are interested in the mechanisms by which beta-cells respond to changes in blood glucose concentration with insulin release. In beta-cells insulin is carried in vesicles, called large dense core vesicles (LDCVs). The mechanics of the transport and fusion of LDCVs are one of the steps that go wrong in type 2 diabetes. Our recent studies have revealed that LDCVs move along their tracks driven by motor proteins such as conventional kinesin. This project aims to understand how the activity of these proteins is regulated by glucose. The spatial-temporal relationship between LDCVs and conventional kinesin movements in response to nutrients will be studied using real time imaging. The role of glucose-stimulated protein kinases and phosphatases in controlling LDCV and kinesin movements and their impact on the association of kinesin with vesicles will be investigated. Novel beta-cell specific kinesin interacting proteins, that link kinesin to LDCVs, will be identified together with the signalling pathway(s) involved in the mobilisation of LDCVs. This multidisciplinary project will reveal fundamental information on the molecular mechanism and regulation of glucose-stimulated LDCV mobilisation. Stimulation of this process may provide novel strategies for the treatment of type 2 diabetes.

Field of science

  • /medical and health sciences/clinical medicine/endocrinology/diabetes
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /social sciences/social and economic geography/transport

Call for proposal

FP7-PEOPLE-2007-2-1-IEF
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

UNIVERSITY OF THE WEST OF ENGLAND, BRISTOL
Address
Frenchay Campus, Coldharbour Lane
BS16 1QY Bristol
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 168 256,91
Administrative Contact
Paul Gough (Prof.)