Hypersecretion of truncated glucagon-like peptide-1 and gastric inhibitory polypeptide in obese patients.

Postprandial insulin secretion is modulated by both neural and humoral gastrointestinal insulinotropic factors in addition to the absorbed nutrient. To investigate the involvement of the potent insulinotropic hormones gastric inhibitory polypeptide (GIP) and truncated glucagon-like peptide-1 (tGLP-1) in the postprandial hyperinsulinaemia of obesity, we examined the changes in plasma levels of GIP and tGLP-1 by an oral glucose tolerance test (OGTT) in nine normal subjects (controls), nine obese subjects without glucose intolerance (Group A), and six obese mild diabetic patients (Group B). Following the OGTT, plasma GIP levels in Group B were increased more markedly than those in the other two groups. Plasma levels of tGLP-1 were estimated by the difference between the values measured with the N-terminal directed antiserum (GLP-1NT) and those with the C-terminal directed antiserum (GLP-1 CT). Plasma levels of GLP-1 NT were increased in Group B, but decreased in the other two groups. Plasma GLP-1 CT levels were increased in all groups with the highest response in Group B. These results suggest that the combined augmentation of plasma GIP and tGLP-1 responses were involved in the delayed and considerable increases in plasma insulin after glucose ingestion in obese diabetic patients. Since tGLP-1 is suppressed in the hyperglycaemic hyperinsulinaemic state in normal subjects, the augmented tGLP-1 response appears to be characteristic of obese Type 2 diabetes.