MRC PhD student
 Level of study: MSc
Title: An in vitro study of the effects of free fatty acids on insulin mediated glucose uptake and metabolism by myocytes and fibroblast derived adipocytes.
Project summary: Elevated levels of free fatty acids (FFAs) are associated with the development of insulin resistance, obesity, chronic inflammation and type 2 diabetes mellitus. Exposure of muscle cells to saturated free fatty acids, especially the long-chain fatty acids such as palmitate and stearate, result in the accumulation of fatty-acid derived cytosolic lipid metabolites which lead to insulin resistance and inflammation. The monounsaturated fatty acid, oleate, ameliorates saturated FFA-induced insulin resistance in the muscle. In contrast to muscle cells, adipocytes are refractory to saturated FFA-induced insulin desensitizing effects and act compensatory to muscle. As muscle and adipose tissue are the major sites of energy utilization, the effect of FFAs on these cells play a major role in the development and pathogenesis of type 2 diabetes. This study will elucidate the interaction of different saturated and unsaturated FFAs on energy utilization and mRNA expression of genes related to insulin signaling and glucose uptake in C2C12 and L8 muscle and 3T3-L1 adipose cells.
The objectives of the study are as follows:
- To assess the effect of the saturated and unsaturated free fatty acids (palmitate, stearate, oleate, omega 3 and omega 6) on insulin signaling in C2C12, L8 muscle and 3T3 adipocyte cell lines.
- To quantify the effect of these FFAs at different concentrations on glucose metabolism (glucose transport activity, glycogen synthesis and glucose oxidation) in C2C12 and L8 muscle and 3T3-L1 adipocytes.
- To determine what effect these free fatty acids have on the mRNA gene expression of Insulin receptor substrate 1, Insulin receptor substrate 2, glucose transporter 4 and Phosphoinositide 3-kinase.
Supervisors: Dr. C.J.F. Muller, Prof. A. Opoku
Study Institution:University of Zululand
MRC Unit: Diabetes Discovery Platform |
