GLP-1 and GIP : hormones of the entero-insular axis.

Sensitive radioimmunoassays for glucagon-like peptide-1 (GLP-1) and human gastric inhibitory polypeptide (GIP) were developed. The assay for GLP-1 was used to demonstrate species-specific differences in the molecular forms of this hormone in the pancreas and intestine of rats and pigs. Post-prandial increases in plasma GLP-1 concentrations were observed in human subjects following carbohydrate, fat, protein and mixed meals. The magnitude and timing of the increases were consistent with GLP-1 acting as a physiological incretin in man. Following a mixed meal, short bowel subjects, who exhibited impaired incretin effects, were found to have normal or slightly elevated plasma GIP concentrations but low plasma GLP-1 concentrations compared control subjects. This provided further evidence that GLP-1 may act as an incretin in man. Plasma GLP-1 concentrations were measured for the first time in species other than man. Pigs were found to exhibit substantially greater post-prandial GLP-1 responses than were observed in man. The novel GIP assay and an established GIP assay, employing an antiserum raised against porcine GIP, detected similar plasma GIP concentrations in human subjects. Following a mixed meal, plasma GIP concentrations, measured with either assay, were found to be similar in lean and obese subjects. This suggests that GIP does not play an important role in the development of hyperinsulinaemia in obesity. A series of experiments were carried out to investigate various physico-chemical factors which may influence the rate and extent of starch digestion and the consequent plasma glucose, insulin, GIP and GLP-1 responses to starch in man. The results obtained suggested that, for most cooked foods, resistant starch content and degree Of starch gelatinization are unlikely to play important roles in determining starch digestibility but that the structural integrity of grains may.