Gould Lab @ Strathclyde
Regulation of Glucose Transport
Our work focusses upon mechanisms of membrane trafficking in health and disease, with emphasis on the control of glucose transporters and how this is disturbed in diabetes and cardiovascular disease.
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Gould Lab @ Strathclyde
A major consequence of insulin action is a dramatic increase in the rate of glucose transport into fat and muscle. This is achieved by the delivery of the facilitative glucose transporter GLUT4 from insulin-sensitive intracellular stores to the cell surface. Insulin-stimulated glucose transport is impaired in Type-2 diabetes; this is underpinned by reduced delivery of GLUT4 to the cell surface. Metabolic disorders such as Type-2 diabetes are linked to the development of cardiovascular disease. Cardiovascular disease represents the single biggest cause of death in T2DM and is independent of concurrent vascular disease.
Studies in our group seek to understand the cellular and molecular mechanisms which regulate glucose transport in adipocytes, cardiomyocytes and skeletal muscle. We focus upon the molecular machinery that control GLUT4 function, its interaction with the insulin signalling system, and defining how these systems are impaired in disease.
Our lab uses a range of experimental systems and approaches. These include studies of cultured adipocytes and genome-edited adipocytes, and iPSC-derived cardiomyocytes as our work-horse models, and employ approaches including imaging techniques such as confocal microscopy and dSTORM, analysis of signalling and trafficking in subcellular fractions and analysis of transport kinetics in intact cells. We also employ Saccharomyces cerevisiae as a tool to study membrane trafficking.
Projects
Projects are available in many areas, including those shown below.
Dynamics of proteins in the plasma membrane
We are using advanced microscopy to study the dynamics of membrane protein behaviour at the surface of physiologically relevant cell types. We have identified complex behaviours of some proteins that we believe underlie their function and our work is resolving the molecular basis of how this behaviour is regulated.
Controlling SNARE complex formation
SNARE proteins are involved in all membrane trafficking events in mammalian cells. Specific interactions between SNARE proteins on the target membrane (t-SNAREs) with cognate SNAREs on the vesicle membrane (v-SNAREs) provides the minimal machinery required for membrane fusion. Regulation of SNARE complex function is a key control mechanism in membrane trafficking events.
Diabetes UK-funded work in our lab studies how insulin regualtes SNARE complex formation.
Trafficking pathways for GLUT4
Insulin stimulates glucose transport in fat and muscle cells by triggering regulated delivery of intracellular vesicles containing the GLUT4 glucose transporter to the plasma membrane. This process is defective in diseases such as Type-2 Diabetes, underscoring the need to define trafficking pathways of GLUT4 and the molecular mechanisms that regulate them. Our work seeks to understand how GLUT4 trafficking is controlled in health and disease.
Adipokines: mechanism of release and functional characterisation
Fat cells secrete an array of adipokines - these have effects on other cells and tissues. Our work studies how these adipokines are released, how this is regulated and what the adipokines do.
Role of Exosomes in insulin resistance
Factors circulating in the serum of patients with diabetes can cause cells to become 'insulin resistant'. We are studying the role of exosomes and adipocytokines in this phenomenon.
Publications
GLUT4 expression and glucose transport in human induced pluripotent stem cell-derived cardiomyocyte
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Peter's graduate work examined how iPSC-derived cardiomyocytes transport glucose.
Which vSNARE is most important for GLUT4 translocation? Jessica asked the question...
Shannan Foylan
BBSRC-funded postdoc
Angéline Geiser
EPSRC-funded PhD student
Group Leader
Justin Greig
PhD student funded by Medical Research Scotland
Technician and Lab Guru
EPSRC postdoc
[joint with Sebastian van de Linde]
Get in Touch
Strathclyde Institute of Pharmacy and Biomedical Sciences,
University of Strathclyde,
161 Cathedral Street, Glasgow G4 0RE
44-141-548-4805
