Lecture: Insulin resistance, Warburg effects and liver cancer

This lecture described the pathways associated with extra/intracellular purinergic signaling, and the relationship to neoplasia.  Adenosine triphosphate (ATP) mediates multiple physiological reactions and plays a crucial role in cellular metabolism.  Adenosine mediates immune suppression and is generated by the ectonucleotidases CD39 (ENTPD1). CD39/ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1) is the dominant ectonucleotidase expressed by most endothelial cells in the liver.

In the case of insulin resistance (example, CD39 knockout model), one intracellular signaling pathway is compromised, though a second pathway is enhanced.  This second pathway leads to increased cellular proliferation (and neoplasia).  The available metabolic breakdown products like lactate, although energy-poor compared to the amount of ATP generated by the Krebs cycle, provides enough ATP to sustain a tumor cell.  This process is known as the Warburg effect. 

For more information about these processes, click on the links below: 

Article 1, from Neoplasia (Mar. 2011) titled- Vascular CD39/ENTPD1 Directly Promotes Tumor Cell Growth by Scavenging Extracellular Adenosine Triphosphate.

Article 2, from Gastroenterology (Sept. 2010) titled- CD39/ENTPD1 Expression by CD4Foxp3+ Regulatory T Cells PromotesHepatic Metastatic Tumor Growth in Mice

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050864/?tool=pubmed

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WFX-50CV7VM-1-M&_cdi=6806&_user=1625289&_pii=S0016508510007353&_origin=gateway&_coverDate=09%2F30%2F2010&_sk=998609996&view=c&wchp=dGLzVlz-zSkWA&md5=2050a42ec11365c4617b8af85ab1dad2&ie=/sdarticle.pdf

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