Effect of human pancreastatin peptide (hP-16) on oral glucose tolerance in man

The gastrointestinal peptide, pancreastatin, has been shown to inhibit insulin release and exocrine pancreatic secretion in the rat. Human pancreastatin-like peptides first isolated from a carcinoid tumor, are expressed in human islets of Langerhans. To investigate the influence of human pancreastatin-16 (hP-16) on oral glucose tolerance (OGTT) in non-diabetic humans, we synthesized the C-terminally amidated human pancreastatin peptide. Healthy male volunteers (n = 6) received in a double-blind placebo-controlled study a 75 g standard OGTT during the i.v. infusion of hP-16 (10 pmol/kg/min) or saline over a time period of 3 h. Peak glucose levels (mg/dl) declined from 151.4 +/- 10.3 (control) to 122.5 +/- 9.7 (hP-16) (mean +/- SEM), peak insulin levels (microU/ml) from 46.3 +/- 2.9 (hP-16) to 32.2 +/- 4.0 (control) and peak C-peptide levels (pmol/ml) from 1.9 +/- 0.1 (hP-16) to 1.2 +/- 0.1 (control). Integrated incremental glucose, insulin and C-peptide responses were reduced by 47% (p < 0.001), 23% (p < 0.05) and 15% (p < 0.05), respectively. In conclusion, these findings indicate that hP-16 attenuates the elevation of blood glucose and insulin levels after an oral glucose load in non-diabetic humans.