Stimulation of secretion of gastric inhibitory polypeptide and insulin by intraduodenal amino acid perfusion

Abstract

The effect of intraduodenal or intravenous administration of a 30-gm mixed amino acid solution of serum gastric inhibitory polypeptide (GIP), alpha-amino nitrogen (AAN), glucose, and insulin concentrations was studied in 10 normal subjects. Initially, an intraduodenal amino acid perfusion (15 ml per min X 60 min) was performed in each subject and was followed in 1 to 2 weeks by an intravenous infusion. Peak AAN concentrations occurred at 60 min after both routes of administration, but were greater with intravenous infusion, 145 +/- 5.7 mug per ml vs. 89 +/- 4.4 mug per ml (P less than 0.001). Although serum AAN levels were significantly lower after intraduodenal administration, incremental insulin concentrations were greater after intraduodenal perfusion, 77.3 +/- 8.8 muM per ml vs. 43.1 +/- 5.6 muU per ml (P less than 0.005). Total integrated insulin secretion was also greater after intraduodenal amino acids, 5000 vs. 2400 muU-min ml-1 (P less than 0.005). With intravenous amino acid infusion, serum GIP concentrations remained below the assay detection limit. After intraduodenal perfusion, a mean maximum GIP increment of 468 pg per ml occurred at 15 min. In all subjects peak GIP concentrations occurred at 15 min and preceded the maximum insulin rise by 15 to 30 min. Total integrated GIP secretion was significantly greater after intraduodenal amino acid perfusion, 13,000 pg-min ml-1 vs. no measurable response with intravenous infusion. In separate studies performed in 12 subjects, no significant changes in serum GIP concentrations occurred after intraduodenal perfusion of 0.45% saline, 0.9% saline, or 10% mannitol. The results of this study demonstrate that intraduodenal amino acid administration stimulates the secretion of GIP and suggest that endogenously released GIP may be important in the enteric mediated release of insulin.