Role of transverse tubules in insulin stimulated muscle glucose transport

Abstract

Although the strongest evidence for recruitment of glucose transporters in response to insulin comes from studies with adipocytes, studies in muscle seem in general to confirm that glucose transporters are also translocated to the cell membrane in muscle in response to insulin. However, the observation that transverse tubule (T-tubule) membranes contain approximately five times more glucose transporter than sarcolemma raised a question as to where glucose transport occurs in muscle. The T-tubule membrane system is continuous with the surface sarcolemma and is a tubule system in which extracellular fluid is in proximity with the interior of the muscle fiber. The purpose of this Prospects article is to evaluate the possibility that the T-tubule membrane may represent a major site of glucose transport in skeletal muscle. Using immunocytochemical techniques we have located GLUT4 glucose transporters on the T-tubule membrane and in vesicles near T-tubules. Since T-tubules form channels into the interior of the muscle fiber, glucose could diffuse or be moved by some peristaltic-like pumping action into the transverse tubules and then be transported across the membrane deep into the interior of the muscle fiber. This mode of transport directly into the interior of the cell would be advantageous over transport across the sarcolemma and subsequent diffusion around the myofibrils to reach the interior of the muscle. Thus, in addition to the role of the T-tubule in ion fluxes and contraction, this unique membrane system can also provide a pathway for the delivery of substrates into the center of the muscle cell where many glycolytic enzymes and glycogen deposits are located.