A high-capacity assay for activators of glucose incorporation into glycogen in L6 muscle cells.

Skeletal muscle is the major tissue responsible for insulin-stimulated glucose uptake and incorporation into glycogen. Skeletal muscle insulin resistance and the resulting postprandial hyperglycemia are hallmarks of non-insulin-dependent diabetes. Therefore, compounds that serve as insulin mimetics or insulin sensitizers in skeletal muscle may be effective in the treatment of diabetes. In order to identify such hypoglycemic agents, a novel assay for activators of glucose incorporation into glycogen has been developed utilizing differentiated L6 muscle cells in 96-well plates. We found that glucose incorporation occurs in a time- and concentration-dependent manner. It is inhibitable by phloretin, an inhibitor of glucose transport. Both insulin and the insulin-mimetic compound pervanadate activate L6 cell glucose incorporation in dose-responsive manners. We conclude that this assay should serve as a high-capacity screen to identify novel compounds that upregulate glucose anabolic metabolism in skeletal muscle. Such chemical entities may prove useful as antidiabetic agents. Copyright 1998 Academic Press.