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20022022
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Personal profile

Research interests

My main research interests are in the areas of insulin and exercise signalling, insulin resistance and glucose metabolism in physiological and pathophysiological conditions. My research brings new cellular and molecular approaches to study the pathophysiology of chronic metabolic conditions and helps understand the impact of nutritional and physiological changes on the development and treatments of insulin resistance, type 2 diabetes and metabolic syndrome.

For several years now, I have investigated the mechanism of glucose transporter (GLUT4) vesicle trafficking. Insulin signalling plays a pivotal role in this process. Therefore, mapping GLUT4 trafficking is critical to understanding the cellular defects in diabetes. The identification of the key molecules linking insulin signalling and GLUT4 trafficking is a major challenge in the GLUT4 research field. The reason this challenge remains is mainly due to the complexity of the insulin-signalling cascade. The next major challenge in this area is to identify the small GTPases of the Rab family of proteins responsible for insulin induced GLUT4 translocation. This is the aim of my current research grant from the MRC.

To achieve this aim I am using a cross-disciplinary approach, combining cellular and molecular studies with a human intervention study in order to translate the molecular findings into whole body physiological functions. We are using cellular models of adipose cells to investigate the molecular interactions between Rab3 and other proteins in the cell that act as links between insulin action at its receptor and the GLUT4 transporter. We will investigate how these interactions are affected by treatment with proinflammatory cytokines, including TNFα, or other molecules known to induce the state of insulin resistance. These experiments will allow us to understand the mechanisms of action of Rab3 in the context of the development of the insulin-resistant state. We will also investigate in humans, undergoing a diet and exercise intervention programme, whether Rab3 is affected in a manner that reveals underlying mechanisms involved in the control of insulin sensitivity in adipose tissues and skeletal muscles. The outcome from this project will have important implications for our understanding of the mechanisms of the development of peripheral tissues insulin resistance and for the development of new, targeted therapies for treatment of insulin resistant subjects and people with type 2 diabetes. This study will also be a springboard to inform further investigations into the development of insulin resistance and the cross-talk between chronic inflammation, obesity and the onset of type 2 diabetes.

Willing to supervise PhD

Identification of new biomarkers of insulin resistance and type 2 diabetes.
Development of human skeletal muscle satellite cell model for in vitro assessment of metabolic health.

Education/Academic qualification

Doctor of Philosophy, Université Grenoble Alpes

Keywords

  • QP Physiology
  • Glucose metabolism
  • glucose transporters
  • Diabetes
  • Insulin signalling
  • Insulin resistance
  • Rab GTPases
  • membrane trafficking
  • skeletal muscle
  • adipocyes
  • obesity
  • Type 2 diabetes
  • GLUT4
  • Cell Biology
  • Biochemistry
  • Tissue culture
  • exocytosis
  • endocytosis

Fingerprint Fingerprint is based on mining the text of the person's scientific documents to create an index of weighted terms, which defines the key subjects of each individual researcher.

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Projects 2009 2022

Insulin
Membrane Fusion
Blood Glucose
Glucose Transporter Type 4
Glucose

Research Output 2002 2019

Fructose and metabolic health: governed by hepatic glycogen status?

Hengist, A., Koumanov, F. & Gonzalez, J., 5 Apr 2019, In : The Journal of Physiology. p. 1-13 13 p.

Research output: Contribution to journalSpecial issue

Open Access
3 Citations (Scopus)
Open Access
Abdominal Subcutaneous Fat
Breakfast
Adipose Tissue
Fasting
Insulin
4 Citations (Scopus)
Open Access
Breakfast
Fasting
Eating
Exercise
Glucose
10 Citations (Scopus)
Open Access
File
Adipose Tissue
Exercise
Adipokines
Messenger RNA
AMP-Activated Protein Kinases
14 Citations (Scopus)

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
File
Tankyrases
Inhibitory Concentration 50
Protein Isoforms
Binding Sites
Glucose

Datasets

Dataset for 'Pre-Exercise Breakfast Ingestion versus Extended Overnight Fasting Increases Postprandial Glucose Flux after Exercise in Healthy Men: Pre-exercise feeding and postprandial glucose flux'

Edinburgh, R. (Creator), Hengist, A. (Creator), Smith, H. (Creator), Travers, R. (Creator), Koumanov, F. (Creator), Betts, J. (Creator), Thompson, D. (Creator), Walhin, J. (Creator), Wallis, G. (Creator), Hamilton, D. L. (Creator), Stevenson, E. (Creator), Tipton, K. (Creator), Gonzalez, J. (Creator), University of Bath, 27 Feb 2019

Dataset

Thesis

Investigating GLUT4 Trafficking in Muscle

Author: Fazakerley, D., 1 Jan 2010

Supervisor: Holman, G. (Supervisor) & Koumanov, F. (Supervisor)

Student thesis: Doctoral ThesisPhD

File

Investigation of Rab-GAPs as links between insulin signalling and GLUT4 translocation

Author: Roche, L., 16 Nov 2013

Supervisor: Holman, G. (Supervisor) & Koumanov, F. (Supervisor)

Student thesis: Doctoral ThesisPhD

File

Novel Proteins Associated with GLUT4 Vesicle Subcellular Traffic

Author: Pereira, V., 16 Sep 2014

Supervisor: Holman, G. (Supervisor) & Koumanov, F. (Supervisor)

Student thesis: Doctoral ThesisPhD

File