Mechanism of elevated serum pancreatic polypeptide concentrations in chronic renal failure

Basal serum concentrations of pancreatic polypeptide (PP) in five patients with chronic renal failure (CRF; 165-2100 pmol/liter) were significantly (P less than 0.01) higher than those in six age-matched normal control subjects (18-54 pmol/liter). Ingestion of a mixed meal resulted in significantly (P less than 0.01) larger increases in serum PP in patients with CRF (245-1740 pmol/liter) than in the normal subjects (72-196 pmol/liter). The iv administration of somatostatin (125 micrograms as a bolus injection, followed by infusion of 125 micrograms/h) to two patients with CRF and two normal subjects completely abolished postprandial PP release. By administering the same dose of somatostatin 60 min after ingestion of the meal, the disappearance rate of endogenously released PP could be estimated. The half-life of disappearance for PP in patients with CRF (t1/2 = 13.2 +/- 1.8 min) was significantly (P less than 0.01) increased compared to that in the normal subjects (t1/2 = 5.6 +/- 0.8 min). Sephadex G-50 column chromatography of basal sera from three patients with CRF revealed three major peaks of PP: one eluting in the void volume, one coeluting with the 4200 molecular weight human PP standard, and one in between. The PP peak coeluting with standard PP comprised 64 +/- 3% of total PP immunoreactivity. Ingestion of food, followed by subsequent infusion of somatostatin, resulted in marked changes in the PP peak coeluting with standard PP, while the two larger molecular forms remained relatively unchanged. At least three findings may be related to the mechanism of elevated serum PP concentrations in patients with CRF: 1) the presence of large molecular forms of PP, 2) a slower disappearance rate for postprandially released PP, and 3) increased postprandial secretion of PP indicating hyperresponsiveness of PP cells to physiological stimuli.