Inhibition of gastric secretion by fat and hypertonic glucose in the dog: role of gastric inhibitory peptide.

1. The gastric and intestinal phases of gastric secretion were selectively evoked by 'meals' of 5% liver extract or saline in five dogs provided with a special cannula that allowed complete separation of the stomach from the duodenum. 2. The gastric phase in response to liver extract administered into the stomach amounted to an increase in acid output equivalent to about 70% of the maximum output in response to histamine. There was also a significant rise in the concentration of gastrin but not of gastric inhibitory peptide (GIP) in the serum. 3. The addition of fat (2 or 4% corn oil) or glucose (20%) to this liver extract meal inhibited secretion of gastric acid by 50 and 30%, respectively, without affecting the concentration of gastrin or GIP in the serum. 4. The 5% liver extract in the duodenum stimulated an increase in gastric acid output amounting to about 40% of the maximum response to histamine. Serum gastrin and GIP levels were not affected. Additional fat (0.5-4.0%) or glucose (10-20%) reduced acid secretion under these conditions by between 50 and 80% without affecting serum gastrin concentrations. Significant increases in the concentration of GIP in the serum occurred in response to intraduodenal glucose (5%), and to fat at the highest dose used (4%). 5. Intraduodenal infusions of glucose (5-20%) significantly increased serum GIP levels. Gastric secretion in response to 5% liver extract in the stomach was significantly inhibited at the highest dose (10 or 20%) although gastrin release was unaffected. 6. These results show that intraduodenal fat and glucose both exhibit potent inhibitory effects on post-prandial gastric acid secretion but that there is no correlation between the changes in serum GIP concentration and the inhibition of gastric secretion under these conditions. 7. We conclude that GIP is unlikely to mediate fat-induced inhibition of gastric secretion, but it is still possible that it might be involved in the inhibition that occurs during intestinal perfusion with hypertonic glucose solutions.