INHIBITION OF GLUCOSE-UTILIZATION IN ISOLATED RAT SOLEUS MUSCLE BY PSEUDOURIDINE - IMPLICATIONS FOR RENAL-FAILURE

Pseudouridine (psi) is an outstanding nucleoside which is not rebuilt into the tRNA once the parent tRNA is broken down. Psi inhibits basal glucose utilization in isolated rat soleus muscle with intact membrane With AD50 42 mumol/l and C(max) 66%. Psi at concentrations found in renal failure patients inhibits both the insulin- and tolbutamide-stimulated glucose utilization. Its inhibitory activity is partially additive with diltiazem inhibition and nonadditive in the case of magnesium depletion. It is concluded that psi inhibits glucose utilization at the level of Ca modulation in the insulin regulatory cascade.