Acute incretin response to oral glucose is associated with stimulation of gastric inhibitory polypeptide, not glucagon-like peptide in young subjects.
Oral glucose induces a greater insulin response than i.v. glucose, a difference apparently due to the secretion of gut factors ("incretins"). Studies examining the mechanisms of this finding in human subjects are limited, however, because of differences in glucose profiles. To overcome this obstacle, we studied eight young nonobese subjects using the hyperglycemic clamp with and without superimposed ingestion of oral glucose. In both studies, glucose was acutely raised by 12.5 mg/dL above fasting values by the infusion of i.v. glucose and maintained at this level for 180 min. During the experimental study, but not the control, each subject ingested oral glucose (30 g) at 120 min, and the glucose infusion was adjusted to maintain the plasma glucose plateau. Plasma insulin responses were nearly identical during both studies until oral glucose was added. After oral glucose, both plasma insulin and C-peptide levels sharply increased by 45-55% above control values (p < 0.001), indicating a potentiation of insulin secretion rather than decreased hepatic extraction of insulin. Plasma gastric inhibitory polypeptide (GIP) levels increased significantly in response to oral glucose, whereas plasma levels of glucagon-like peptide-1 (7-37) were not affected. The time course of the rise in plasma GIP and insulin was nearly identical. We conclude that the GIP response to a modest oral glucose load may play an important physiologic role in glucose-stimulated insulin secretion in healthy young subjects.
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Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Tamborlane
W V
WV
Sherwin
R S
RS
Pederson
R
R
Caprio
S
S
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000097:blood; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D005947:Glucose; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D010446:Peptide Fragments / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects; D013268:Stimulation, Chemical
D002096:C-Peptide; D005768:Gastrointestinal Hormones; D010446:Peptide Fragments; D010455:Peptides; C055453:glucagon-like peptide 1 (7-36)amide; D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose