Transient, early release of glucagon-like peptide-1 during low rates of intraduodenal glucose delivery.
BACKGROUND
The "incretin" hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), account for some 60% of the stimulation of insulin by oral glucose, but the determinants of their secretion from the small intestine are poorly understood. Cells which release GIP (K cells) are localized to the proximal small intestine, while GLP-1 releasing cells (L cells) predominate in the distal gut. It has been suggested that a threshold rate of duodenal glucose delivery (approximately 1.8 kcal/min) needs to be exceeded for stimulation of GLP-1.


OBJECTIVE
To determine whether a low intraduodenal glucose load (1 kcal/min) has the capacity to stimulate GLP-1, and if so, the characteristics of the response.


METHODS
Retrospective analysis of all studies in our laboratory involving healthy humans administered intraduodenal glucose at 1 kcal/min for 120 min.


METHODS
Clinical research laboratory.


METHODS
27 healthy subjects (24 male; age 36+/-3 years; BMI 25.2+/-0.7 kg/m(2)).


METHODS
Plasma GLP-1, GIP, insulin, and blood glucose concentrations, reported as mean+/-SEM.


RESULTS
During intraduodenal glucose, plasma GLP-1 increased at 15 and 30 min (P<0.001 for both) and returned to baseline thereafter. In contrast, there were sustained increases in plasma GIP (P<0.001), insulin (P<0.001), and blood glucose (P<0.001).


CONCLUSIONS
In healthy subjects, there is early, transient stimulation of GLP-1 by glucose loads hitherto believed to be "sub-threshold". The mechanisms underlying this effect, which could be attributed to initially rapid transit to jejunal L cells, or a duodeno-jejunoileal neural or hormonal loop, remain to be determined.
Kuo
Paul
P
University of Adelaide, Discipline of Medicine, Royal Adelaide Hospital, Australia.
Chaikomin
Reawika
R
Pilichiewicz
Amelia
A
O'Donovan
Deirdre
D
Wishart
Judith M
JM
Meyer
James H
JH
Jones
Karen L
KL
Feinle-Bisset
Christine
C
Horowitz
Michael
M
Rayner
Christopher K
CK
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D004386:Duodenum / Q000187:drug effects; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis / Q000097:blood*; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007421:Intestine, Small / Q000187:drug effects; D007441:Intubation, Gastrointestinal; D008297:Male; D012189:Retrospective Studies
D001786:Blood Glucose; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005947:Glucose