Comparative Study of the Effects of Porcine Proinsulin and Insulin on Lipolysis and Glucose Oxidation in Rat Adipocytes

Abstract

Proinsulin blocked lipolysis activation by epinephrine, glucagon or theophylline. The antilipolytic effect of pro-insulin was not blocked by Kunitz pancreatic trypsin inhibitor (KPTI). The-concentrations of proinsulin and insulin required to cause 50 per cent inhibition of epinephrine-stimulated lipolysis were estimated to be approximately 1 × 10−9 M and 3 × 10−11 M respectively. Proinsulin which had been reduced and allowed to reoxidize was found to have approximately the same antilipolytic activity as native proinsulin, indicating that the antilipolytic effect was due to proinsulin and not insulin contamination. The concentrations of proinsulin and insulin required to give 50 per cent of maximal stimulation of glucose oxidation were estimated to be approximately 5 × 10−9 M and 1 × 10−11 M respectively. The effect of proinsulin on glucose oxidation did not appear to be caused by any insulin contamination since reduced-reoxidized proinsulin had approximately the same activity as native proinsulin. KPTI had no effect on proinsulin-stimulated glucose oxidation in isolated fat cells, in contrast to the marked inhibitory effect observed using intact epididymal fat pad. This suggests that the KPTI-sensitive proteolytic activity of the epididymal fat pad is not located in the fat cell but in some other type cell or extracellular space.