The exaggerated glucagon-like peptide-1 response is important for the improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes

Nils B Jørgensen; Carsten Dirksen; Kirstine N Bojsen-Møller; Siv H Jacobsen; Dorte Worm; Dorte L Hansen; Viggo B Kristiansen; Lars Naver; Sten Madsbad; Jens Juul Holst

doi:10.2337/db13-0022

The exaggerated glucagon-like peptide-1 response is important for the improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes

Nils B Jørgensen, Carsten Dirksen, Kirstine N Bojsen-Møller, Siv H Jacobsen, Dorte Worm, Dorte L Hansen, Viggo B Kristiansen, Lars Naver, Sten Madsbad, Jens Juul Holst

197 Citations (Scopus)

Abstract

β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving β-cell function and glucose tolerance and regulating glucagon release after RYGB using exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R)specific antagonist. Nine patients with type 2 diabetes were examined before and 1 week and 3 months after surgery. Each visit consisted of two experimental days, allowing a meal test with randomized infusion of saline or Ex-9. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased, and glucagon secretion was augmented. GLP-1R blockade did not affect β-cell function or meal-induced glucagon release before the operation but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased, and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance for the improvement in β-cell function, control of glucagon release, and glucose tolerance in patients with type 2 diabetes.

Original language	English
Journal	Diabetes
Volume	62
Issue number	9
Pages (from-to)	3044-3052
Number of pages	9
ISSN	0012-1797
DOIs	https://doi.org/10.2337/db13-0022
Publication status	Published - Sept 2013

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Jørgensen, N. B., Dirksen, C., Bojsen-Møller, K. N., Jacobsen, S. H., Worm, D., Hansen, D. L., Kristiansen, V. B., Naver, L., Madsbad, S., & Holst, J. J. (2013). The exaggerated glucagon-like peptide-1 response is important for the improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes. Diabetes, 62(9), 3044-3052. https://doi.org/10.2337/db13-0022

The exaggerated glucagon-like peptide-1 response is important for the improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes. / Jørgensen, Nils B; Dirksen, Carsten; Bojsen-Møller, Kirstine N et al.
In: Diabetes, Vol. 62, No. 9, 09.2013, p. 3044-3052.

Research output: Contribution to journal › Journal article › Research › peer-review

Jørgensen, NB, Dirksen, C, Bojsen-Møller, KN, Jacobsen, SH, Worm, D, Hansen, DL, Kristiansen, VB, Naver, L, Madsbad, S & Holst, JJ 2013, 'The exaggerated glucagon-like peptide-1 response is important for the improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes', Diabetes, vol. 62, no. 9, pp. 3044-3052. https://doi.org/10.2337/db13-0022

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title = "The exaggerated glucagon-like peptide-1 response is important for the improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes",

abstract = "β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving β-cell function and glucose tolerance and regulating glucagon release after RYGB using exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R)specific antagonist. Nine patients with type 2 diabetes were examined before and 1 week and 3 months after surgery. Each visit consisted of two experimental days, allowing a meal test with randomized infusion of saline or Ex-9. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased, and glucagon secretion was augmented. GLP-1R blockade did not affect β-cell function or meal-induced glucagon release before the operation but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased, and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance for the improvement in β-cell function, control of glucagon release, and glucose tolerance in patients with type 2 diabetes.",

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AU - Bojsen-Møller, Kirstine N

AU - Jacobsen, Siv H

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N2 - β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving β-cell function and glucose tolerance and regulating glucagon release after RYGB using exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R)specific antagonist. Nine patients with type 2 diabetes were examined before and 1 week and 3 months after surgery. Each visit consisted of two experimental days, allowing a meal test with randomized infusion of saline or Ex-9. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased, and glucagon secretion was augmented. GLP-1R blockade did not affect β-cell function or meal-induced glucagon release before the operation but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased, and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance for the improvement in β-cell function, control of glucagon release, and glucose tolerance in patients with type 2 diabetes.

AB - β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving β-cell function and glucose tolerance and regulating glucagon release after RYGB using exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R)specific antagonist. Nine patients with type 2 diabetes were examined before and 1 week and 3 months after surgery. Each visit consisted of two experimental days, allowing a meal test with randomized infusion of saline or Ex-9. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased, and glucagon secretion was augmented. GLP-1R blockade did not affect β-cell function or meal-induced glucagon release before the operation but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased, and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance for the improvement in β-cell function, control of glucagon release, and glucose tolerance in patients with type 2 diabetes.

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The exaggerated glucagon-like peptide-1 response is important for the improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes

Abstract

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