Regulation of islet hormone release and gastric emptying by endogenous glucagon-like peptide 1 after glucose ingestion.
BACKGROUND
Exogenous administration of glucagon-like peptide (GLP)-1 improves glucose tolerance by stimulation of insulin secretion, inhibition of glucagon secretion, and delay of gastric emptying. It is not known which of these effects is involved in the action of endogenous GLP-1 to control blood glucose. To determine the role of endogenous GLP-1 on islet cell function and gastric emptying independent of variable glycemia, we clamped blood glucose before and during glucose ingestion with and without GLP-1 receptor blockade with exendin-[9-39] (Ex-9).


METHODS
There were 10 healthy subjects that participated in two experiments each, one a control and one with infusion of 750 pm/kg . min Ex-9. Subjects consumed 75 g oral glucose solution mixed with d-xylose and (13)C-glucose while their blood glucose levels were held fixed at approximately 8.9 mmol/liter.


RESULTS
Plasma insulin levels during hyperglycemia alone were similar in the two studies (control, 282.5 +/- 42 vs. Ex-9, 263.8 +/- 59 pmol/liter) but were reduced by approximately 30% by Ex-9 after glucose ingestion (control, 1154 +/- 203 vs. Ex-9, 835 +/- 120 pmol/liter; P < 0.05). Blocking the action of endogenous GLP-1 caused an approximate 80% increase in postprandial glucagon concentrations. The appearance of ingested d-xylose in the blood was not affected by Ex-9, suggesting that postprandial secretion of GLP-1 has only minimal effects on gastric emptying of oral glucose.


CONCLUSIONS
These findings indicate that GLP-1 is an incretin in healthy humans at modestly supraphysiological blood glucose levels. The primary effect of GLP-1 to regulate oral glucose tolerance is mediated by effects on islet hormones and not on gastric emptying.
Salehi
Marzieh
M
Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, Ohio 45267, USA. salehim@uc.edu
Vahl
Torsten P
TP
D'Alessio
David A
DA
D000328:Adult; D000465:Algorithms; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005746:Gastric Emptying / Q000235:genetics* / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010187:Pancreatic Hormones / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors; D014994:Xylose / Q000097:blood / Q000494:pharmacology
D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010187:Pancreatic Hormones; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D014994:Xylose; D005947:Glucose