Role of transverse tubules (T-tubules) in muscle glucose transport

Abstract

The first data to demonstrate glucose transporter translocation in muscle used membranes enriched in sarcolemma because it was assumed that this was the equivalent of the cell membrane of adipocytes. We studied translocation in intact human muscle using immunogold labeling of the GLUT4 transporter but found very little labeling on the sarcolemma. In contrast, there was abundant gold-labeling associated with the T-tubules and we proposed that glucose transport occurred across this membrane system. In a subsequent study using an entirely different technique, we labeled cell surface glucose transporters of rat muscle with a cell impermeant photolabel and demonstrated that a majority of the glucose transporters were translocated to T-tubules, not to the sarcolemma, in response to insulin. In this report we show for the first time that in insulin-plus contraction stimulated muscle, GLUT4 glucose transporters are associated with an area that we call the SCT complex (Sarcolemmal, Caveoli, T-tubule complex). This SCT complex may play an important role in delivering metabolites to the muscle under conditions, such as muscle contraction, when there is a very high requirement for glucose transport. From our data, and supporting data from other labs, we propose that the T-tubule membrane system plays a very important role in delivering nutrients to the center of skeletal muscle cells. Substrates can be quickly carried to the center of the muscle fiber where there are proteins to transport glucose (and presumably other substrates) across the T-tubule membrane to the site where it can be immediately utilized or stored. This hypothesis deserves serious consideration and experimental testing.