The enteroinsular axis.

Rediscovery of the role of the gastrointestinal tract in the control of carbohydrate metabolism and, as we now know, fat and protein metabolism, was made independently in London by two groups of workers (Dupre, 1964a; McIntyre et al., 1964). The major credit undoubtedly belongs to McIntyre and his colleagues (1964, 1965) who, by the simplest of methods, namely comparing the glycaemic and insulinaemic responses to equal amounts of glucose given by intravenous and intrajejunal infusion, and using only two subjects initially, were able to show that the gut mediated an augmentation of the insulinaemic response to hyperglycaemia. Despite an enormous amount of effort by many workers since that time, it is still not possible to attribute, with any degree of certainty, the role of intestinal augmenter of glucose-stimulated insulin release to any one agency. Nervous factors undoubtedly play a role but will not be considered here. Of the many hormonal agents that have been proposed, some meet the bill better than others. For the sake of brevity I shall exclude from further consideration those which I believe play only a minor or non-existent role and concentrate upon those substances that I have personally been most concerned with or consider to be potentially physiologically important, namely glucagon, gut glucagon-cross-reacting material, or GLI (often, perhaps inappropriately, referred to as enteroglucagon), insulin-releasing polypeptide (IRP) and GIP.' Several comprehensive reviews are available and interested readers are referred to them (Marks and Samols, 1970; Marks and Turner, 1977).