Cycloheximide (20-200 mg/l) did not affect basal D-[U-14C]
xylose uptake by rat soleus muscle (2.4 +/- 0.2 mumol . g-1 . h-1). However, the stimulatory effect of
insulin on
sugar transport was progressively reduced from 375% above basal in control muscles to 170% in muscles exposed to 200 mg
cycloheximide/l but above this concentration
cycloheximide inhibited basal
xylose uptake without further effect on the incremental effect of
insulin.
Cycloheximide affected the
insulin dose-response curve both by depressing
insulin sensitivity and by reducing the maximum stimulatory effect of the
hormone. In contrast to the inhibition of
insulin action, which increased progressively over the range 20-200 mg
cycloheximide/l,
muscle protein synthesis was inhibited maximally at a concentration of 10 mg/l.
Cycloheximide also inhibited the insulinomimetic effects of
anoxia, 2:4-dinitrophenol,
salicylate, cooling,
hydrogen peroxide,
diamide,
vitamin K5, hyperosmolarity and
EDTA, but did not affect
concanavalin A-stimulated
xylose uptake. It is concluded that
cycloheximide inhibits
insulin-stimulated
sugar transport at some late post-receptor step, and that this effect of
cycloheximide is not secondary to the inhibition of
protein synthesis.