Modulation of hepatic reticuloendothelial system phagocytosis by pancreatic hormones.

Abstract

Experiments were conducted to determine the influence of the pancreatic hormones insulin, glucagon, and somatostatin on reticuloendothelial system (RES) phagocytosis both in vivo and in the isolated perfused livers of rats. Chronic pancreatic hormonal treatment consisted of twice daily injections SC of NPH insulin with doses ranging from 0.75 U on day 1 to 9.0 U on day 13 and unchanged doses of glucagon (200 micrograms) and somatostatin (50 micrograms). Chronic treatment with insulin significantly depressed by 48% intravascular phagocytosis of colloidal carbon administered IV at a dose of 8 mg/100 g, while glucagon and somatostatin stimulated macrophage endocytic function by 32% and 26%, respectively, compared to the control value. Acute treatment with the three pancreatic hormones at 30 min prior to carbon administration similarly produced insulin depression as well as glucagon and somatostatin stimulation of RES phagocytosis. Addition of the three hormones at near physiologic concentrations (20 ng/ml for insulin, 10 ng/ml for glucagon, and 5 ng/ml for somatostatin) to the recirculating perfusate of isolated perfused rat livers simultaneous with 24 mg of colloidal carbon likewise resulted in phagocytic reduction after insulin and enhancement after glucagon and somatostatin. Experiments involving insulin in vitro with isolated perfused livers as well as glucose replacement therapy concomitant with insulin in vivo demonstrated that hypoglycemia is not necessary for phagocytic depression by insulin while severe hypoglycemia in the perfusion medium is sufficient to depress carbon uptake by isolated perfused livers independent of insulin. Both pancreatic hormones and the level of glycemia seem to be important in modulating hepatic reticuloendothelial system phagocytosis.