Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass.
OBJECTIVE
Roux-en-Y gastric bypass (RYGB) improves glycaemic control in part by increasing postprandial insulin secretion through exaggerated glucagon-like peptide (GLP)-1 release. However, it is unknown whether islet cell responsiveness to i.v. glucose, non-glucose (arginine) and incretin hormones, including GLP-1, is altered.


METHODS
Eleven severely obese glucose-tolerant individuals underwent three hyperglycaemic clamps with arginine bolus and co-infusion of either GLP-1, glucose-dependent insulinotropic polypeptide (GIP) or saline before, and at 1 week and 3 months after RYGB. In addition, an OGTT was performed before and 3 months after surgery.


RESULTS
After RYGB, insulin sensitivity improved at 1 week and 3 months, while insulin stimulation and glucagon suppression in response to the clamp with saline co-infusion were largely unaltered. The influence of i.v. GLP-1 and GIP on insulin and glucagon secretion was also unchanged postoperatively. In response to the postoperative OGTT at 3 months, insulin and GLP-1, but not GIP, secretion increased. Furthermore, the glucose profile during the OGTT was altered, with a substantial reduction in 2 h plasma glucose and a paradoxical hypersecretion of glucagon.


CONCLUSIONS
After RYGB, insulin hypersecretion is linked to the oral, but not the i.v., route of administration and is associated with exaggerated release and preserved insulinotropic action of GLP-1, while both the secretion and action of GIP are unchanged. The results highlight the importance of increased GLP-1 secretion for improving postoperative glucose metabolism.


BACKGROUND
ClinicalTrials.gov NCT01559779.
Department of Endocrinology, Hvidovre Hospital, Kettegaard Allé 30, 2650, Hvidovre, Denmark, carsten.dirksen@hvh.regionh.dk.
Carsten
C
Dirksen
Kirstine N
KN
Bojsen-Møller
Nils B
NB
Jørgensen
Siv H
SH
Jacobsen
Viggo B
VB
Kristiansen
Lars S
LS
Naver
Dorte L
DL
Hansen
Dorte
D
Worm
Jens J
JJ
Holst
Sten
S
Madsbad
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D015390:Gastric Bypass; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D015309:Glucose Clamp Technique / Q000379:methods; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D009767:Obesity, Morbid / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D010179:Pancreas / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D019518:Postprandial Period; D016896:Treatment Outcome
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; C049962:gastric inhibitory polypeptide (1-39); D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon