EFFECT OF IN-VIVO INJECTION OF CHOLERA AND PERTUSSIS TOXIN ON GLUCOSE-TRANSPORT IN RAT SKELETAL-MUSCLE

Cholera toxin (CTX) and pertussis toxin (PTX) were examined for their ability to inhibit glucose transport in perfused skeletal muscle. Twen ty-five hours after an intravenous injection of CTX, basal transport w as decreased similar to 30%, and insulin- and contraction-stimulated t ransport was reduced at least 86 and 49%, respectively, in both the so leus and red and white gastrocnemius muscles. In contrast, PTX treatme nt was much less efficient. impairment of glucose transport appeared t o develop 10-15 h after CTX administration, which coincided with devel opment of hyperglycemia despite hyperinsulinimia, increased plasma fre e fatty acid levels, increased adenosine 3',5'-cyclic monophosphate (c AMP) concentrations in muscle, but no difference in plasma catecholami nes. Twenty-five hours after CTX treatment, GLUT-4 protein in both sol eus and red gastrocnemius muscles was decreased, whereas no change in GLUT-1 protein content was found. In contrast, GLUT-4 mRNA was unchang ed, but transcripts for GLUT-1 were increased greater than or equal to 150% in all three muscles from CTX-treated rats. The findings suggest that CTX via increased cAMP impairs basal as well as insulin- and con traction-stimulated muscle glucose transport, at least in part from a decrease in intramuscular GLUT-4 protein.