Thesis Ruth Meex

Lipid accumulation in skeletal muscle; big deal?

Mechanisms underlying the development of insulin resistance

Global prevalence and incidence rates of type 2 diabetes are very high and increase rapidly. It has been estimated that in 2000 approximately 171 million individuals were diag-nosed with type 2 diabetes and this number is likely to double by 2030. Type 2 diabe-tes is characterized by high plasma glucose levels and results from a reduction in insulin secretion from the pancreas, and from a blunted sensitivity (i.e. resistance), of tissues for insulin, the hormone responsible for glucose uptake into the cells. The underlying mechanism of insulin resistance is not yet known. Accumulation of in-tramyocellular lipids (IMCL) has been associated with the severity of insulin resis-tance. However, endurance trained athletes also have high IMCL levels while being highly insulin sensitive, making IMCL accumulation per se less plausible as a cause for the development of insulin resistance. It has therefore been suggested that other parameters, such as impaired mitochondrial function, a decreased ability to switch between glucose oxidation and fat oxidation (metabolic inflexibility) and a decreased ability to store glucose, are also important in development of muscle insulin resis-tance. This PhD-thesis focuses on theses parameters as well as on their role in rela-tion to the development of the insulin resistant state.
                                                                    Ruth Meex, September 8th 2011