Hypoglycaemic effect of proinsulin and insulin in intact and eviscerated rats

The hypoglycaemic potency of biosynthetic human proinsulin and human insulin was studied in intact anaesthetized rats and in eviscerated hepatectomized rats, the latter serving as model for an in vivo muscle/fat tissue preparation. Intravenous dose response curves demonstrated a similar about 5-times smaller potency of proinsulin in both experimental conditions (half-maximal effective dose in intact rats for insulin 3.5, for proinsulin 17.5 nM/kg body weight; in eviscerated rats for insulin 3.6, for proinsulin 18.5 nM/kg). In intact rats hepatic glycogen content 2 h after hormone injection was higher in proinsulin than in insulin treated animals despite similar preceding hypoglycaemia which might suggest a preferential inhibitory action of proinsulin on hepatic glycogen breakdown (135 mumol glycosyl units/g liver for proinsulin-injected and 82 mumol glycosyl units/g liver for insulin-injected rats at half-maximal hypoglycaemia).