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Glucose intolerance is often associated with pancreatitis. Pancreatitis-induced diabetes represents a different clinical syndrome than type I and type II diabetes mellitus. Patients with pancreatitis-induced diabetes may be extremely sensitive to exogenous insulin, rarely develop ketoacidosis, and rarely exhibit classic diabetic complications, such as retinopathy, nephropathy, or accelerated vasculopathy. Pancreatic polypeptide (PP) deficiency has been implicated in the defect of glucose homeostasis found after pancreatitis. This study evaluated intravenous and oral glucose tolerance and insulin response to glucose loading, in the setting of pancreatitis, with and without short-term PP replacement. Dogs (n = 7) underwent pancreatic duct ligation (PDL) and were studied with and without PP infusion (2 micrograms/kg/hr) before PDL and at 1 week, 6 weeks, and 4 months after PDL by means of intravenous and oral glucose tolerance tests. Basal and bombesin-stimulated PP levels at 4 months after PDL were subnormal, verifying PP deficiency in these animals with pancreatitis. PP levels during PP infusion reproduced normal postcibal levels, averaging 897 +/- 40 pg/ml. Glucose tolerance, expressed as the glucose decay constant for the intravenous glucose tolerance tests and as the integrated glucose response for the oral glucose tolerance tests, deteriorated over time and was not improved by acute PP replacement. The integrated insulin response to glucose was not affected by PP. The acute infusion of PP at a dose that reproduces normal postprandial PP levels fails to improve glucose tolerance or augment insulin release in this model of pancreatitis-induced diabetes.

Pancreatic polypeptide (PP) deficiency has been associated with impaired hepatic sensitivity to insulin and pancreatogenic diabetes in chronic pancreatitis. Since pancreatic resection might also result in PP deficiency, hepatic responses to insulin infusion (0.25 mU/kg/min) were determined by the euglycemic glucose clamp technique in 10 patients who had previously undergone pancreatic resection for trauma and in eight healthy control subjects. Six resection patients (RES-PP) demonstrated deficient PP levels, with a mean increase of plasma immunoreactive PP of 20 +/- 7 pg/ml above basal rate after a test meal compared with 232 +/- 82 pg/ml in control subjects (p less than 0.01) and 353 +/- 133 pg/ml in four other patients undergoing resection with normal levels of immunoreactive PP (RES + PP) (p less than 0.03). Three identical insulin infusion studies were performed in each subject, the second of which was performed during the final 2 hours of an 8-hour infusion of bovine PP (2.0 pmol/kg/min). Whereas hepatic glucose production (HGP) in control subjects fell 74% +/- 4% from a basal rate of 2.0 +/- 0.1 mg/kg/min to a 60- to 120-minute value of 0.5 +/- 0.1 mg/kg/min during insulin infusion, HGP was suppressed only 58% +/- 5% in RES-PP subjects, from 1.9 +/- 0.1 to 0.8 +/- 0.1 mg/kg/min (p less than 0.05 vs controls). Intravenous infusion of PP corrected the hepatic resistance to insulin seen in the PP-deficient group. During PP infusion, HGP was suppressed 74% +/- 5% in RES-PP subjects, from 2.1 +/- 0.2 to 0.5 +/- 0.1 mg/kg/min (p less than 0.04 compared with initial study). PP infusion produced no significant change in glucose metabolism in control and RES + PP subjects. Overall glucose disposal rates were not altered by PP infusion in any group. These findings support a role of PP as a glucoregulatory hormone and suggest that PP deficiency may serve as a reversible pathophysiologic factor in the abnormal glucose metabolism seen after pancreatic resection.