Reversal of abnormal glucose metabolism in chronic pancreatitis by administration of pancreatic polypeptide

Chronic pancreatitis, induced in dogs by pancreatic duct ligation, is associated with glucose intolerance due to insulin deficiency, reduced hepatic sensitivity to insulin, and a marked deficiency of pancreatic polypeptide. Treatment with a 14 day continuous subcutaneous infusion of pancreatic polypeptide resulted in improved oral glucose tolerance and improved hepatic glucose responses to insulin in dogs with chronic pancreatitis. No effect of continuous subcutaneous infusion of pancreatic polypeptide was seen in the control dogs. The time course of the effect of continuous subcutaneous infusion on the hepatic response to insulin was relatively immediate, whereas the effects on improvement in oral glucose tolerance were prolonged. We conclude that pancreatic polypeptide may function physiologically to enhance the hepatic glucose response to insulin and that alterations in glucose metabolism seen in chronic pancreatitis may be due, in part, to a deficiency in pancreatic polypeptide. Since treatment with continuous subcutaneous infusion of pancreatic polypeptide restored the hepatic response to insulin and oral glucose tolerance to more normal levels in our animal model, administration of pancreatic polypeptide may play a therapeutic role in the treatment of certain forms of pancreatogenic diabetes.