GLUCOSE TRANSPORTERS AND IN-VIVO GLUCOSE-UPTAKE IN SKELETAL AND CARDIAC-MUSCLE - FASTING, INSULIN STIMULATION AND IMMUNOISOLATION STUDIES OF GLUT1 AND GLUT4

Our aim was to study glucose transporters GLUT1 and GLUT4 in relation to in vivo glucose uptake in rat cardiac and skeletal muscle. The leve ls of both transporters were of a similar order of magnitude in whole muscle tissue (GLUTI/GLUT4 ratio varied from 0.1 to 0.6), suggesting t hat both may have an important physiological role in regulating muscle glucose metabolism. GLUT4 correlated very strongly (r2 = 0.97) with m aximal insulin-stimulated glucose uptake (Rg(max.)', estimated using t he glucose clamp plus 2-deoxy[H-3]glucose bolus technique) in six skel etal muscles and heart. A distinct difference in regulation of the two transporters was evident in heart: in 5 h-fasted rats, basal glucose uptake and GLUTI levels in heart were very high and both were reduced, by 90 and 60 % respectively, by 48 h fasting. However, in heart (and in red skeletal muscle), neither GLUT4 levels nor Rg(max.)' were reduc ed by 48 h fasting. GLUT1 was shown to be specifically expressed in ca rdiac myocytes, because intracellular vesicles enriched in GLUT4 conta ined significant levels of GLUT1. In conclusion, the high association of muscle GLUT4 content with insulin responsiveness in different muscl es, and the preservation of both with fasting, supports a predominant role of GLUT4 in insulin-mediated glucose uptake. GLUT1 may play an im portant role in mediating cardiac muscle glucose uptake in the basal m etabolic state. Marked changes in GLUT1 expression with alterations in the metabolic state, such as prolonged fasting, may play an important role in cardiac glucose metabolism.