AIMS/HYPOTHESIS: The incretin effect describes the augmentation of postprandial insulin secretion by gut hormones. It is not known whether glucagon secretion is also influenced by an incretin effect. A glucagon suppression deficiency has been reported in some patients with type 2 diabetes, but it is unclear whether this abnormality is present prior to diabetes onset. We therefore addressed the questions: (1) Is glucagon secretion different after oral and during intravenous glucose administration? (2) If so, is this related to the secretion of incretin hormones? (3) Is glucagon secretion abnormal in first-degree relatives of patients with type 2 diabetes? MATERIALS AND METHODS: We examined 16 first-degree relatives of patients with type 2 diabetes and ten matched control subjects with an oral glucose load (75 g) and with an 'isoglycaemic' intravenous glucose infusion. RESULTS: Glucagon levels were significantly suppressed by both oral and intravenous glucose (p < 0.0001), but glucagon suppression was more pronounced during intravenous glucose administration (76 +/- 2%) than after oral glucose administration (48 +/- 4%; p < 0.001). The differences in the glucagon responses to oral and i.v. glucose were correlated with the increments in gastric inhibitory polypeptide (GIP) (r = 0.60, p = 0.001) and glucagon-like peptide (GLP)-1 (r = 0.46, p < 0.05). There were no differences in glucagon levels between first-degree relatives and control subjects. CONCLUSIONS/ INTERPRETATION: Despite the glucagonostatic actions of GLP-1, the suppression of glucagon secretion by glucose is diminished after oral glucose ingestion, possibly due to the glucagonotropic actions of GIP and GLP-2. Furthermore, in this group of first-degree relatives, abnormalities in glucagon secretion did not precede the development of other defects, such as impaired insulin secretion.
AIMS/HYPOTHESIS: The incretin effect describes the augmentation of postprandial insulin secretion by gut hormones. It is not known whether glucagon secretion is also influenced by an incretin effect. A glucagon suppression deficiency has been reported in some patients with type 2 diabetes, but it is unclear whether this abnormality is present prior to diabetes onset. We therefore addressed the questions: (1) Is glucagon secretion different after oral and during intravenous glucose administration? (2) If so, is this related to the secretion of incretin hormones? (3) Is glucagon secretion abnormal in first-degree relatives of patients with type 2 diabetes? MATERIALS AND METHODS: We examined 16 first-degree relatives of patients with type 2 diabetes and ten matched control subjects with an oral glucose load (75 g) and with an 'isoglycaemic' intravenous glucose infusion. RESULTS:Glucagon levels were significantly suppressed by both oral and intravenous glucose (p < 0.0001), but glucagon suppression was more pronounced during intravenous glucose administration (76 +/- 2%) than after oral glucose administration (48 +/- 4%; p < 0.001). The differences in the glucagon responses to oral and i.v. glucose were correlated with the increments in gastric inhibitory polypeptide (GIP) (r = 0.60, p = 0.001) and glucagon-like peptide (GLP)-1 (r = 0.46, p < 0.05). There were no differences in glucagon levels between first-degree relatives and control subjects. CONCLUSIONS/ INTERPRETATION: Despite the glucagonostatic actions of GLP-1, the suppression of glucagon secretion by glucose is diminished after oral glucose ingestion, possibly due to the glucagonotropic actions of GIP and GLP-2. Furthermore, in this group of first-degree relatives, abnormalities in glucagon secretion did not precede the development of other defects, such as impaired insulin secretion.