Suppression of glucagon secretion is lower after oral glucose administration than during intravenous glucose administration in human subjects.
OBJECTIVE
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?


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
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.
Meier
J J
JJ
Department of Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791, Bochum, Germany. juris.meier@rub.de
Deacon
C F
CF
Schmidt
W E
WE
Holst
J J
JJ
Nauck
M A
MA
D000284:Administration, Oral; D000328:Adult; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000737:chemistry; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose