Abstract
Using an established radioimmunoassay for immunoreactive gastric inhibitory polypeptide (IR-GIP) the metabolic actions of gastric inhibitory polypeptide (GIP) were investigated. It was found that there was no circadian rhythm in basal plasma IR-GIP and immunoreactive insulin (IRI) concentrations in normal human volunteers, but that there was in stimulated IR-GIP and IRI plasma concentrations following a mixed meal. It was shown that short-term adaptation of both humans and rats, with high-fat diets, could cause moderate insulin resistance as demonstrated by the removal of the feed-back inhibition of exogenous insulin on fat-stimulated IR-GIP release. It was shown that GIP via its role in the enteroinsular axis, might play a part in the development of the hyperinsulinaemia and obesity of the genetically obese hyperglycaemic (ob/ob) mouse. It was demonstrated that the pre-requisite for fat-stimulated IR-GIP release in the ob/ob mouse is the absorption of fatty acids and glycerides capable of being esterified into triglyceride. Any physical, chemical or metabolic interference with this process resulted in a decrease of the amount of IR-GIP released. It was further shown, using a combination of both exogenous and endogenous lipid and GIP, that GIP has a role in the removal of chylomicron triglyceride from the circulation of the rat. It was not possible to confirm this in humans using exogenous lipid and endogenous glucose-stimulated IR-GIP release. It was shown in the insulinoma bearing NEDH rat that exogenous porcine GIP was able to augment the insulin stimulating ability of glucose when co-administered intravenously with glucose, thus providing strong evidence for GIP's role as an incretin.