The actin cytoskeleton and glucose metabolism
Optimal skeletal muscle glucose uptake is essential in order to maintain glycemic control. A loss of insulin sensitivity (insulin resistance) elevates blood glucose levels and increases the risk of developing type 2 diabetes. Exercise is a powerful stimulus for skeletal muscle glucose uptake and has been found to increase insulin sensitivity (2; 6). Because the insulin- and exercise-mediated signalling cascades are distinct yet interacting, exercise can be used as a preventative modality for insulin resistance. However, the intracellular mechanisms by which insulin and exercise increase skeletal muscle glucose uptake are not fully understood.
Recent work has shown that the actin-cytoskeleton is a major regulator of insulin-stimulated glucose uptake, by facilitating translocation of intracellular glucose transporters (GLUT4) to the cell surface in cell culture (1; 3; 5). In addition, the GTPase Rac1 has been shown to be involved in the regulation of actin remodelling during such events and found to be essential for insulin to stimulate glucose uptake in mouse and rat skeletal muscle (4; 7; 8).
We are exploring Rac1 regulation in skeletal muscle cell lines (C2C12 and L6) and in intact tissue to investigate if Rac1 and the actin cytoskeleton is regulating insulin and contraction-stimulated glucose uptake. By this we aim to expand our understanding of the underlying mechanism of glucose metabolism in skeletal muscle.
Head of project: Lykke Sylow
Supervisor: Erik Richter