AJP - Endocrinology and Metabolism, Vol 252, Issue 2 E248-E254, Copyright © 1987 by American Physiological Society
Polymyxin B selectively inhibits insulin effects on transport in isolated muscle
T. Gremeaux, J. F. Tanti, E. Van Obberghen and Y. Le Marchand-Brustel
Polymyxin B (PMB), a cyclic decapeptide antibiotic, inhibits the
hypoglycemic effect of insulin in vivo. To elucidate the mechanism of PMB
action, we have studied its effect in vitro on insulin-stimulated pathways
in the mouse skeletal muscle. PMB, added to the incubation mixture,
specifically inhibited insulin-stimulated 2-deoxyglucose transport and
alpha-aminoisobutyric acid uptake in the isolated soleus muscle but did not
affect the basal rates of transport (measured in the absence of insulin).
PMB did not alter insulin binding and hexokinase activity. PMB effect was
observed at all deoxyglucose concentrations tested, and PMB was also able
to inhibit vanadate-stimulated glucose transport. By contrast, insulin
activation of glycogen synthase was not prevented by PMB. Basal and
maximally insulin-stimulated insulin receptor tyrosine kinase activity,
tested in a cell-free system, was similar for both autophosphorylation and
phosphorylation of exogenous substrates in the absence or in the presence
of PMB. Furthermore, the insulin sensitivity of the kinase was increased in
the presence of PMB. Our results suggest that the anti-insulin effect of
PMB observed in vivo is due to an inhibition of insulin-stimulated glucose
transport in the skeletal muscle perhaps through a specific blockade of the
insulin-induced translocation of the glucose carriers.
