Professor Gwyn Gould, from the Division of Molecular and Cell
ular Biology, University of Glasgow, has submitted his final report to DRWF following the Open Funding grant awarded to him in 2009.
The DRWF grant was awarded for the research project titled, 'Analysis of the role of Munc18c tyrosine phosphorylation in insulin-stimulated glucose transport'.
The premise behind the research was that insulin stimulates glucose transport into fat and muscle by promoting the movement of specialised transporter proteins from an internal storage depot to the cell surface. These transporter proteins function as specialised doorways through which glucose can move from the blood into fat and muscle for storage after a meal. By increasing the number of 'doorways' present in the boundary membrane of cells, insulin drives glucose into storage organs. This key action of insulin is known to be impaired in type 2 diabetes.
The project was directed towards understanding how insulin controls the insertion of these doorways into the boundary membrane. This movement of glucose doorways to the cell surface is mediated by a trafficking process. Insulin regulates this process by controlling the activity of the fusion proteins, and the hypothesis of the research was that insulin controls this machinery, which the project set out to confirm.
The data gained from the research offers the hypothesis that insulin-stimulated tyrosine phosphorylation of Munc18 may be a crucial facet of insulin action.
In laymans terms, it suggests that a key feature of the control mechanism which facilitates the insertion of the glucose doorways into cell surface membranes, is the ability of insulin to reversibly modify one protein (Munc18c) and so remove a ‘break’ on the fusion process.
Professor Gould said, 'The grant from DRWF allowed us to refine this model, to generate new experimental data in support of this, and also to begin to develop a powerful new approach to study the interactions of the machinery in living cells. It is the latter which is particularly exciting'.
His next objective will be to seek full project grant support to develop the assay further and to refine the model for how insulin controls the activity of the fusion machinery.