The binding and biologic potencies as well as kinetics of action of human biosynthetic
proinsulin (HPro) were studied in primary cultures of rat hepatocytes. HPro had 3%
(on a molar basis) of the potency of porcine insulin for displacing (125I)-TyrA14-insulin from receptors. Maximally effective concentrations of insulin and HPro caused
similar stimulations of 14C-glucose incorporation into glycogen and glycogen synthase activity. However, the
dose response curve for HPro stimulation of glycogen synthase was shifted far to the
right (EC50 = 4.1 ± 1.1 nM) of that for insulin (.09 ± .01). The relative biologic potency of
HPro was ˜ 3%. Biologically equivalent maximal doses of insulin (8.3 nM) and HPro
(53.2 nM) stimulated glycogen synthase activity with similar time courses; half maximal
between 15-30 min with maximal effects at 60 min. Deactivation of glycogen synthase
upon removal of the hormone was very rapid for both hormones. The relative binding
and biologic potencies of HPro compared to insulin in liver (˜ 3%) were similar to
values previously seen in adipocytes. This fact, together with the similarity of kinetics
of action, suggest that the in vivo hepatoselectivity of HPro is not a property of
the target cell itself.
Insulin Action - Proinsulin - Glycogen Synthase - Hepatocytes
