MRC MSc student

Level of study: MSc

Title: β-cell response to high fat diet induced metabolic demands in the obese Wistar rat.

Project summary: Obesity due to overnutrition and physical inactivity is associated with a higher risk for developing type 2 diabetes.  Exposing rats to a high fat diet induces obesity and peripheral insulin resistance.  Despite the progression of this metabolic disorder, hyperglycaemia is avoided in rats until advanced age. In the rat, pancreatic β-cell regeneration and expansion compensates for the increased metabolic demand.  This research will contribute to understanding the mechanisms whereby pancreatic β-cell mass is increased in obese individuals.  Furthermore, this study will provide insight into β-cell neogenesis and expansion in adult subjects. Elucidation of these compensatory mechanisms could provide potential therapies for type 2 diabetes.

The objectives of the study are:

• To establish the effect of high fat feeding on carbohydrate metabolism and determine the degree of insulin resistance in obese Wistar rat; 
• Study β-cell mass dynamics including proliferation and apoptosis rates in response to the diet;
• Determine glucose sensing in pancreatic β-cells and hepatocytes by measuring GLUT2 expression; and
• Demonstrate the cellular origin of β-cell neogenesis using early β-cell transcription factors including PDX-1, SOX-9, MAFA and NGN3. 

Supervisors: Drs. C.J.F. Muller, M.E. Cerf and Prof B.J. Page
Study Institution:University of Stellenbosch
MRC Unit: Diabetes Discovery Platform