[Protamine sulfate-induced resistance to the hypoglycemic effect of insulin]

Administration of protamine sulfate in a dose (0.9-1.1 mg/200 g) sufficient for binding reactive circulatory heparin provokes in rats the status of temporary resistance to the hypoglycemic action of both exogenous and endogenous insulin. This effect occurs after protamine sulfate administration 5-30 minutes prior to insulin in doses of 0.2-2.4 Units/200 g, respectively, or release of endogenous heparin stimulated by sugar load. As the time interval between administration of protamine sulfate and administration (release) of insulin is prolonged or shortened, the status of resistance does not develop. Protamine sulfate does not produce any effect on the blood concentration of immunoreactive insulin. Similarly to protamine sulfate, the resistance to the hypoglycemic action of insulin may be also provoked by the synthetic heparin antagonist, 2,5-ionene that binds heparin, forming a stable polyelectrolyte complex ionene-heparin. Administration of a sufficient heparin dose (10 Units/200 g) may interrupt the protamine sulfate-induced resistance, which manifests in the recurrence of the hypoglycemic action of insulin. There are reasons to assume that the presence of reactive heparin in the circulation is necessary for insulin reception by target tissues.