Mitochondrial dysfunction in type 2 diabetes

Type 2 diabetes is a degenerative disease afflicting modern Western society. Recently, an association was found between mitochondrial function and development of the disease. Abnormal mitochondrial function may, on the one hand, result in a failing cellular energy supply and, on the other, in elevated oxidative stress. Downstream effects of the latter are typically detrimental, impacting cell function both on a microscopic (i.e., damage to proteins and lipids of individual mitochondria and other cell constituents) as well as macroscopic scale (e.g., spatial reorganization of the cellular mitochondrial network).This research project seeks to gain insight into the development of type 2 diabetes by investigating how impaired mitochondrial function impacts cell function on both the microscopic as well as macroscopic scale. Hereto, a systems biology approach, combining computational modeling on the one hand, and low-to-medium throughput quantitative and dynamic measurements on the other, will be applied. All investigations will be conducted in skeletal muscle, one of the main affected tissues in diabetes type 2.The model of Van Stiphout et al 2006 will be adapted and used to test different hypotheses for the development of type 2 diabetes. The alterations will include the addition of the sarcoplasmatic reticulum, radical production in the mitochondrion and possible reduction of the model based on a sensitivity analysis and the results of Van Stiphout et al.