Doktorander/utbildningsplats
Sahlgrenska akademin vid Göteborgs universitet / Apotekarjobb / Göteborg
2010-11-18
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G213 4837/10
Clinical and experimental studies of insulin resistance
Application deadline: 2010-12-08
Description of the research project
The overall aim of this project is to better understand the pathophysiology of insulin resistance for optimising treatment of hyperglycemia in patients with type 2 diabetes. We shall test three hypotheses in human subjects in this program: 1. Transfer of insulin across the vascular wall to the target cells in skeletal muscle and adipose tissue is further impaired in insulin resistant subjects who show hyperglycemia; 2. Microvascular endothelial cells in insulin resistant subcutaneous adipose tissue from these subjects show impairments in the insulin signaling pathway which may provide a molecular mechanism behind the observed "endothelial barrier" for insulin; 3. Per oral phosphodiesterase-5 inhibition (Tablet Cialis , tadalafil) improves vascular function when administered to insulin resistant subjects and may increase transendothelial transport of insulin leading to increased glucose uptake in skeletal muscle and adipose tissue. Accordingly, we shall recruit insulin resistant subjects showing overweight and hyperglycemia, as well as healthy controls and study their interstitial insulin concentrations in skeletal muscle and adipose tissue by the microdialysis technique. Tissue from subcutaneous needle biopsies is used for extraction of endothelial cells by magnetic beads and isolation of fat cells. The extracted endothelial cells are expanded in primary culture and studied with Western blotting and RT-PCR techniques while the same techniques are employed for studies of insulin action in isolated fat cells. To elucidate if we are able to overcome the endothelial barrier for insulin we shall conduct a randomised controlled trial with tadalafil or placebo in hyperglycemic insulin resistant subjects including molecular studies of microvascular endothelial cells and fat cells, monitoring of insulin kinetics and lipolysis in situ by microdialysis as well as assessments of whole body insulin sensitivity by glucose clamp. Collectively, this project explore whether studies of the subcutaneous microvascular endothelium may unravel molecular mechanisms behind the apparent "endothelial barrier" for insulin as demonstrated by microdialysis in situ and, finally, whether phosphodiesterase-5 inhibition may be a new principle to reverse this defect allowing better treatment of hyperglycemia in insulin resistant subjects, typically patients with type 2 diabetes.
For more information about the project, please contact main supervisor Per-Anders Jansson,
per-anders.jansson@medic.gu.sePubliceringsdatum2010-11-18Arbetstider och omfattningVisstidsanställning 6 månader eller längre
Heltid
Så ansöker duSista dag att ansöka är 2010-12-08
Ange följande referens när du ansöker: "G213 4837/10"
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FöretagSahlgrenska akademin vid Göteborgs universitet
AdressSahlgrenska akademin vid Göteborgs universitet
Box 400
40530 GÖTEBORG
KontorsadressMedicinaregatan 3
KontaktuppgifterTelefonnummer: 031-7860000
Jobbnummer 780582
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