Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery
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Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery. / Svane, Maria S; Bojsen-Moller, Kirstine N; Nielsen, Signe; Jørgensen, Nils B; Dirksen, Carsten; Bendtsen, Flemming; Kristiansen, Viggo B; Hartmann, Bolette; Holst, Jens J; Madsbad, Sten.
I: American Journal of Physiology: Endocrinology and Metabolism, Bind 310, Nr. 7, 01.04.2016, s. E505-E514.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery
AU - Svane, Maria S
AU - Bojsen-Moller, Kirstine N
AU - Nielsen, Signe
AU - Jørgensen, Nils B
AU - Dirksen, Carsten
AU - Bendtsen, Flemming
AU - Kristiansen, Viggo B
AU - Hartmann, Bolette
AU - Holst, Jens J
AU - Madsbad, Sten
N1 - Copyright © 2016, American Journal of Physiology - Endocrinology and Metabolism.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Exaggerated secretion of glucagon-like peptide 1 (GLP-1) is important for postprandial glucose tolerance after Roux-en-Y gastric bypass (RYGB), whereas the role of glucose-dependent insulinotropic polypeptide (GIP) remains to be resolved. We aimed to explore the relative importance of endogenously secreted GLP-1 and GIP on glucose tolerance and beta-cell function after RYGB. We used DPP-4 inhibition to enhance concentrations of intact GIP and GLP-1 and the GLP-1 receptor antagonist exendin 9-39 (Ex-9) for specific blockage of GLP-1 actions. Twelve glucose tolerant patients were studied after RYGB in a randomized, placebo-controlled, four-day, cross-over study with standard mixed meal tests and concurrent administration of: placebo, oral sitagliptin, Ex-9 infusion or combined Ex-9/sitagliptin. GLP-1 receptor antagonism increased glucose excursions, clearly attenuated beta-cell function and aggravated postprandial hyperglucagonaemia compared with placebo, whereas sitagliptin had no effect despite 2-3-fold increased concentrations of intact GLP-1 and GIP. Similarly, sitagliptin did not affect glucose tolerance or beta-cell function during GLP-1R blockage. This study confirms the importance of GLP-1 for glucose tolerance after RYGB via increased insulin and attenuated glucagon secretion in the postprandial state, whereas amplification of the GIP signal (or other DPP-4 sensitive glucose lowering mechanisms) did not appear to contribute to the improved glucose tolerance seen after RYGB.
AB - Exaggerated secretion of glucagon-like peptide 1 (GLP-1) is important for postprandial glucose tolerance after Roux-en-Y gastric bypass (RYGB), whereas the role of glucose-dependent insulinotropic polypeptide (GIP) remains to be resolved. We aimed to explore the relative importance of endogenously secreted GLP-1 and GIP on glucose tolerance and beta-cell function after RYGB. We used DPP-4 inhibition to enhance concentrations of intact GIP and GLP-1 and the GLP-1 receptor antagonist exendin 9-39 (Ex-9) for specific blockage of GLP-1 actions. Twelve glucose tolerant patients were studied after RYGB in a randomized, placebo-controlled, four-day, cross-over study with standard mixed meal tests and concurrent administration of: placebo, oral sitagliptin, Ex-9 infusion or combined Ex-9/sitagliptin. GLP-1 receptor antagonism increased glucose excursions, clearly attenuated beta-cell function and aggravated postprandial hyperglucagonaemia compared with placebo, whereas sitagliptin had no effect despite 2-3-fold increased concentrations of intact GLP-1 and GIP. Similarly, sitagliptin did not affect glucose tolerance or beta-cell function during GLP-1R blockage. This study confirms the importance of GLP-1 for glucose tolerance after RYGB via increased insulin and attenuated glucagon secretion in the postprandial state, whereas amplification of the GIP signal (or other DPP-4 sensitive glucose lowering mechanisms) did not appear to contribute to the improved glucose tolerance seen after RYGB.
U2 - 10.1152/ajpendo.00471.2015
DO - 10.1152/ajpendo.00471.2015
M3 - Journal article
C2 - 26786780
VL - 310
SP - E505-E514
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
SN - 0193-1849
IS - 7
ER -
ID: 160636684