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The importance of endogenously secreted GLP-1 and GIP for postprandial glucose tolerance and β-cell function after Roux-en-Y gastric bypass and sleeve gastrectomy surgery

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posted on 2022-12-07, 18:14 authored by Morten Hindsø, Nora Hedbäck, Maria S. Svane, Andreas Møller, Christoffer Martinussen, Nils B. Jørgensen, Carsten Dirksen, Lærke S. Gasbjerg, Viggo B. Kristiansen, Bolette Hartmann, Mette M. Rosenkilde, Jens J. Holst, Sten Madsbad, Kirstine N. Bojsen-Møller

Enhanced secretion of glucagon-like peptide-1 (GLP-1) seems to be essential for improved postprandial β-cell function after Roux-en-Y gastric bypass (RYGB) but is less studied after sleeve gastrectomy (SG). Moreover, the role of the other major incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), is relatively unexplored after bariatric surgery. We studied the effects of separate and combined GLP-1 receptor (GLP-1R) and GIP receptor (GIPR) blockade during mixed meal tests in unoperated (CON), SG-operated, and RYGB-operated people with no history of diabetes. Postprandial GLP-1 concentrations were highest after RYGB but also higher after SG compared with CON. In contrast, postprandial GIP concentrations were lowest after RYGB. The effect of GLP-1R versus GIPR blockade differed between groups. GLP-1R blockade reduced β-cell glucose sensitivity and increased or tended to increase postprandial glucose responses in the surgical groups but had no effect in CON. GIPR blockade reduced β-cell glucose sensitivity and increased or tended to increase postprandial glucose responses in the CON and SG groups but had no effect in the RYGB group. Our results support that GIP is the most important incretin hormone in unoperated people, whereas GLP-1 and GIP are equally important after SG, and GLP-1 is the most important incretin hormone after RYGB.

Funding

The study was conducted at the Department of Endocrinology, Copenhagen University Hospital Hvidovre (Hvidovre, Denmark) and was supported by grants from the Novo Nordic Foundation Excellence Project (NNF18 OC0032330), the Hvidovre Hospital Research Fund, the “Doctor Sofus Carl Emil Friis and Wife Olga Dorus Friis” foundation, and the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 695069-BYPASSWITHOUTSURGERY).

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