Vivid doctoral researchers have discovered a novel mechanism how contraction stimulates glucose uptake in skeletal muscle. It is well known that both insulin stimulation and muscle contraction lead to increased glucose uptake in skeletal muscle through rapid and reversible translocation of GLUT4 glucose transporters from intracellular vesicles to the cell surface. Interestingly, in muscle cells from individuals with type 2 diabetes, insulin-mediated GLUT4 translocation is impaired but contraction-induced translocation of GLUT4 is normal. The molecular mechanism how insulin and contraction signalling interact was unknown.
In the new study, deWendt and coworkers have studied translocation of GLUT4 in knockout mice that lack all the known major signaling proteins for both contraction- and insulin-stimulated GLUT4 translocation, namely AMPK, TBC1D1 and TBC1D4. They discovered an alternative signalling pathway that involves the GTPase Rac1. This pathway appears to link both insulin and contraction-mediated signalling and may provide new opportunities for treating insulin resistance and type 2 diabetes.
Contraction-Mediated Glucose Transport in Skeletal Muscle is Regulated by a Framework of AMPK, TBC1D1/4 and Rac1.
de Wendt C, Espelage L, Eickelschulte S, Springer C, Toska L, Scheel A, Bedou AD, Benninghoff T, Cames S, Stermann T, Chadt A, Al-Hasani H. Diabetes. 2021 Sep 24:db210587. doi: 10.2337/db21-0587. Online ahead of print.PMID: 34561225