ACUTE NON-INSULIN-LIKE STIMULATION OF RAT MUSCLE GLUCOSE-METABOLISM BY TROGLITAZONE IN-VITRO

1 The direct short-term effects of troglitazone on parameters of gluco se metabolism were investigated in rat soleus muscle strips. 2 In musc le strips from Sprague-Dawley rats, troglitazone (3.25 mu mol l(-1)) i ncreased basal and insulin-stimulated glucose transport by 24% and 41% , respectively (P<0.01 each). 3 In the presence of 5 nmol l(-1) insuli n, stimulation of glucose transport by 3.25 mu mol l(-1) troglitazone was accompanied by a 36% decrease in glycogen synthesis, while glycoly sis was increased (112% increase in lactate production) suggesting a c atabolic response of intracellular glucose handling. 4 Whereas insulin retained its stimulant effect on [H-3]-2-deoxy-glucose transport in h ypoxia-stimulated muscle (by 44%; c.p.m. mg(-1) h(-1): 852+/-77 vs 122 9+/-75, P<0.01), 3.25 mu mol l(-1) troglitazone failed to increase glu cose transport under hypoxic conditions (789+/-40 vs 815+/-28, NS) sug gesting that hypoxia and troglitazone address a similar, non-insulin-l ike mechanism. 5 No differences between troglitazone and hypoxia were identified in respective interactions with insulin. 6 Troglitazone acu tely stimulated muscle glucose metabolism in a hypoxia/contraction-lik e manner, but it remains to be elucidated whether this contributes to the long-term antidiabetic and insulin enhancing potential in vivo or is to be regarded as an independent pharmacological effect.