An artificial endocrine pancreas is a mechanical device that frequently measures blood glucose and adjusts the rate of insulin infusion to maintain normoglycemia. In this study, we evaluated the effect of pancreatic polypeptide (PP) on insulin requirements after total pancreatectomy. However, other endocrine hormones are needed not only to facilitate the effect of insulin, but also to regulate insulin functions in vivo. In this study, the effect of PP infusion on insulin requirements after total pancreatectomy in dogs is examined. After total pancreatectomy, five dogs were supported by artificial endocrine pancreas model STG-22 for 72 h. In a second group of five dogs, both insulin and PP were infused. Mean blood glucose levels and insulin requirements were compared between the two groups. There was no difference in mean plasma glucose levels between the two groups. In all 10 dogs, the mean blood glucose level for 72 h was 110 +/- 4 mg/dL and was tightly controlled between 65 and 190 mg/dL. However, the insulin requirement for the first and second postoperative days in the group treated with PP was significantly less than that of the control group (90.0 +/- 20.8 mU/kg vs. 445.0 +/- 151.9 mU/kg; P < 0.05, and 562.7 +/- 126.5 mU/kg vs. 1007.7 +/- 144.9 mU/kg; P < 0.05, respectively). We conclude that infusion of PP reduces the insulin requirement for the initial 48 h in pancreatectomized dogs treated with an artificial endocrine pancreas.