Cholecystokinin-Induced Gallbladder Emptying and Single-Dose Metformin Elicit Additive Glucagon-Like Peptide-1 Responses
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Cholecystokinin-Induced Gallbladder Emptying and Single-Dose Metformin Elicit Additive Glucagon-Like Peptide-1 Responses. / Rohde, Ulrich; Sonne, David Peick; Christensen, Mikkel; Hansen, Morten; Brønden, Andreas; Toräng, Signe; Rehfeld, Jens Frederik; Holst, Jens Juul; Lauritsen, Tina Vilsbøll; Knop, Filip Krag.
In: The Journal of clinical endocrinology and metabolism, Vol. 101, No. 5, 01.05.2016, p. 2076-2083.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Cholecystokinin-Induced Gallbladder Emptying and Single-Dose Metformin Elicit Additive Glucagon-Like Peptide-1 Responses
AU - Rohde, Ulrich
AU - Sonne, David Peick
AU - Christensen, Mikkel
AU - Hansen, Morten
AU - Brønden, Andreas
AU - Toräng, Signe
AU - Rehfeld, Jens Frederik
AU - Holst, Jens Juul
AU - Lauritsen, Tina Vilsbøll
AU - Knop, Filip Krag
PY - 2016/5/1
Y1 - 2016/5/1
N2 - CONTEXT: Bile acids have been suggested to mediate glucagon-like peptide-1 (GLP-1) secretion via activation of the bile acid receptor TGR5 on enteroendocrine L cells. Metformin too has been shown to increase GLP-1 levels. The effect of gallbladder emptying, metformin or a combination has however never been studied.OBJECTIVE: We hypothesized that cholecystokinin-8 (CCK)-induced gallbladder emptying stimulates human GLP-1 secretion and that metformin would potentiate this effect.DESIGN: A double-blinded, randomized study.SETTING: The study was conducted at a specialized research unit.PARTICIPANTS: Ten healthy male subjects with no family history of diabetes (aged 22 (range 20-32) years; body mass index 21.7 (19.3-24.2) kg/m(2); fasting plasma glucose 4.9 (4.7-5.3) mM; and HbA1c 5.1 (4.4-5.8) %).INTERVENTION: On 4 separate days, the subjects received metformin or placebo and a concomitant 60-minute intravenous infusion of saline or CCK. Blood was sampled for 4 hours and gallbladder volume measured by ultrasound.MAIN OUTCOME MEASURES: Plasma levels of GLP-1.RESULTS: CCK-induced gallbladder emptying and metformin alone (no observed effect on gallbladder emptying), both elicited significant and additive GLP-1 responses. Metformin alone or combined with gallbladder emptying elicited a significant peptide YY response. CCK-induced gallbladder emptying resulted in a short-lasting glucose-dependent insulinotropic polypeptide (GIP) response independent of metformin. No effects were seen on plasma glucose, insulin, C-peptide or gastrin.CONCLUSIONS: CCK-induced gallbladder emptying in healthy subjects elicits significant GLP-1 secretion, which can be potentiated by metformin.
AB - CONTEXT: Bile acids have been suggested to mediate glucagon-like peptide-1 (GLP-1) secretion via activation of the bile acid receptor TGR5 on enteroendocrine L cells. Metformin too has been shown to increase GLP-1 levels. The effect of gallbladder emptying, metformin or a combination has however never been studied.OBJECTIVE: We hypothesized that cholecystokinin-8 (CCK)-induced gallbladder emptying stimulates human GLP-1 secretion and that metformin would potentiate this effect.DESIGN: A double-blinded, randomized study.SETTING: The study was conducted at a specialized research unit.PARTICIPANTS: Ten healthy male subjects with no family history of diabetes (aged 22 (range 20-32) years; body mass index 21.7 (19.3-24.2) kg/m(2); fasting plasma glucose 4.9 (4.7-5.3) mM; and HbA1c 5.1 (4.4-5.8) %).INTERVENTION: On 4 separate days, the subjects received metformin or placebo and a concomitant 60-minute intravenous infusion of saline or CCK. Blood was sampled for 4 hours and gallbladder volume measured by ultrasound.MAIN OUTCOME MEASURES: Plasma levels of GLP-1.RESULTS: CCK-induced gallbladder emptying and metformin alone (no observed effect on gallbladder emptying), both elicited significant and additive GLP-1 responses. Metformin alone or combined with gallbladder emptying elicited a significant peptide YY response. CCK-induced gallbladder emptying resulted in a short-lasting glucose-dependent insulinotropic polypeptide (GIP) response independent of metformin. No effects were seen on plasma glucose, insulin, C-peptide or gastrin.CONCLUSIONS: CCK-induced gallbladder emptying in healthy subjects elicits significant GLP-1 secretion, which can be potentiated by metformin.
U2 - 10.1210/jc.2016-1133
DO - 10.1210/jc.2016-1133
M3 - Journal article
C2 - 27003305
VL - 101
SP - 2076
EP - 2083
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 5
ER -
ID: 160444251