Release of gastric inhibitory polypeptide (GIP) by intraduodenal acidification in rats and humans and abolishment of the incretin effect of acid by GIP-antiserum in rats.

Intraduodenal infusion of 0.05-0.5 N hydrochloric acid dose-dependently increases serum levels of immunoreactive gastric inhibitory polypeptide (GIP) in rats. Immunoreactive GIP released by duodenal acidification is biologically active because it augments the glucose-induced release of immunoreactive insulin (IRI). This augmentation of glucose-induced IRI release by intraduodenal acid can be abolished for 30 min by simultaneous intravenous infusion of GIP-antiserum. From this it is concluded that the initial capacity to augment the glucose-induced insulin release (incretin activity) of hydrochloric acid is due to its ability to release GIP. Later on, other gut factors with incretin activity might be released by hydrochloric acid. Also, in humans, intraduodenal infusion of 0.1 N hydrochloric acid releases GIP without changing serum levels of glucose or insulin. The GIP release is a direct effect of intraduodenal acid and is not mediated via secretin release. Injection of secretin in supraphysiologic doses does not change serum levels of immunoreactive GIP. However, such secretin injections induce a short-term insulin release and a decrease in serum glucose concentration.