Effects of Acute Experimental Pancreatitis on Insulin Metabolism in the Dog: Application of a New Equilibrium Infusion Technic

Abstract

Experimental pancreatitis has been induced in dogs by instillation of bile into the pancreatic duct. An equilibrium infusion technic with I-131-insulin has been employed to evaluate the subsequent changes in the plasma levels of immunoreactive insulin (IRI). Evidence for acute intravascular insulinolysis (due to a putative release of pancreatic proteases and/or peptidases into the circulation) could not be demonstrated. Changes compatible with modest, late attenuation in the rates of insulin degradation were observed in some studies. However, in all experiments, the induction of pancreatitis effected prompt increases in total plasma IRI which exceeded concurrent changes in the “steady-state” concentration of infused I-131-insulin. Thus, the elevations of plasma IRI were greater than could be ascribed to alterations in insulin degradation or distribution. Direct analysis of pancreatic venous effluent indicated that the “extra” IRI originated, at least in part, from a purge of preformed pancreatic insulin or immunologically reactive insulin-like material. It displayed the same immunological reactivity on serial dilution as IRI released in response to conventional hyperglycemia. Consideration of the concomitant changes in plasma glucose and FFA during acute pancreatitis suggested that insulin-like effects may be greater in the liver than the periphery.