See related article, pages 1311–1318. fibers express both Glut1 and Glut4, with Glut4 being vastly more abundant (24). As in the adipocyte, Glut4 appears to be responsible for most or all of the insulin-stimulated glucose transport that occurs in muscle fibers (25). In contrast to adipocytes, skeletal muscle fibers contain not one but two distinct plasma membrane domains: the sarcolemma (or plasma membrane proper) and the transverse tubules (t-tubules), special invaginations of the plasma membrane that extend deep into the fiber. T-tubules and the sarcolemma have distinct protein compositions and represent two distinct subcellular targeting domains (26). In skeletal muscle, Glut1 is targeted constitutively to the sarcolemma and is largely excluded from t-tubules, and, unlike in adipocytes, Glut1 is not responsive to insulin (27). In contrast, Glut4 is enriched in membrane structures in the triad region of muscle fibers, where the t-tubules, terminal cisternae, and sarcoplasmic reticulum meet, as well as in the sarcolemma, subsarcolemmal vesicles, and perinuclear Golgi-like membrane structures (27, 28). Insulin stimulates an increase in the density of Glut4 both in the sarcolemma and in ttubules, but the bulk of insulin-stimulated transport appears to occur across t-tubules (27). This latter observation is consistent with quantitative morphological analyses indicating that more than 90% of Glut4 in the insulin-stimulated state is present in t-tubules (27), which generally present a much greater total surface area to the extracellular milieu in muscle fibers than does the sarcolemma. This finding apparently explains how glucose can permeate the dense myofibrillar network and diffuse deep into the muscle fiber, where it is required for ATP production and biosynthetic reactions.