Analysis of Signal Transduction during development of Atherosclerosis in Type II Diabetes mellitus
Christian Müller (PhD-Student)
Diabetes is a disease where the regulation of the blood glucose level is disturbed. Diabetes Mellitus patients often suffer from high blood pressure and other side effects of atherosclerosis, which often takes a deadly course. In contrast to Type I Diabetes a Type II Diabetes mellitus patient's blood contains a lot more insulin when compared to a healthy person. But due to an insulin resistance the hormone is unable or just slightly able to activate the necessary signalling pathways in the target tissues of liver, muscle and fat, for the blood sugar's reduction.
For the successful reduction of blood sugar primarily three signalling pathways are important, which are all initiated due to ligand binding at the insulin receptor. Activation of Phospholipase C, in all cells but neurons, for instance leads to the activation of Phosphofructokinase, which drives the consumption of glucose in the glycolysis. Insulin binding to its receptor via a MAPKinase cascade, incorporating ERK1/2, brings about the activation of Glycogen Synthase, which facilitates the conversion of glucose to glycogen in liver cells. Finally the Insulin Receptor dependent activation of Phosphatidylinositol-3-kinase leads, via Protein Kinase B, to the integration of GLUT4 glucose transporters in the membranes of muscle and fat cells, which highly increases glucose uptake.
Here the pathogenesis of Diabetes mellitus Type II and Atherosclerosis shall be further elucidated via detection of changes of the activity of single members of the above mentioned signalling cascades in adult stem cells, in order to enable the development of therapies in the future.