For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
17
views
38
references
 Top references
cited by
43
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      342
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Exaggerated Glucagon-Like Peptide 1 Response Is Important for Improved β-Cell Function and Glucose Tolerance After Roux-en-Y Gastric Bypass in Patients With Type 2 Diabetes

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references38

          • Record: found
          • Abstract: found
          • Article: not found

          Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes.

          Blandine Laferrère, Julio Teixeira, James J McGinty … (2008)
          Gastric bypass surgery (GBP) results in rapid weight loss, improvement of type 2 diabetes (T2DM), and increase in incretins levels. Diet-induced weight loss also improves T2DM and may increase incretin levels. Our objective was to determine whether the magnitude of the change of the incretin levels and effect is greater after GBP compared with a low caloric diet, after equivalent weight loss. Obese women with T2DM studied before and 1 month after GBP (n = 9), or after a diet-induced equivalent weight loss (n = 10), were included in the study. Patients from both groups were matched for age, body weight, body mass index, diabetes duration and control, and amount of weight loss. This outpatient study was conducted at the General Clinical Research Center. Glucose, insulin, proinsulin, glucagon, gastric inhibitory peptide (GIP), and glucagon-like peptide (GLP)-1 levels were measured after 50-g oral glucose. The incretin effect was measured as the difference in insulin levels in response to oral and to an isoglycemic iv glucose load. At baseline, none of the outcome variables (fasting and stimulated values) were different between the GBP and diet groups. Total GLP-1 levels after oral glucose markedly increased six times (peak:17 +/- 6 to 112 +/- 54 pmol/liter; P < 0.001), and the incretin effect increased five times (9.4 +/- 27.5 to 44.8 +/- 12.7%; P < 0.001) after GBP, but not after diet. Postprandial glucose levels (P = 0.001) decreased more after GBP. These data suggest that early after GBP, the greater GLP-1 and GIP release and improvement of incretin effect are related not to weight loss but rather to the surgical procedure. This could be responsible for better diabetes outcome after GBP.
          Article 0 comments Cited 137 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes.

            P Højberg, S Madsbad, T Vilsbøll … (2009)
            The incretin effect is attenuated in patients with type 2 diabetes mellitus, partly as a result of impaired beta cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The aim of the present study was to investigate whether 4 weeks of near-normalisation of the blood glucose level could improve insulin responses to GIP and GLP-1 in patients with type 2 diabetes. Eight obese patients with type 2 diabetes with poor glycaemic control (HbA(1c) 8.6 +/- 1.3%), were investigated before and after 4 weeks of near-normalisation of blood glucose (mean blood glucose 7.4 +/- 1.2 mmol/l) using insulin treatment. Before and after insulin treatment the participants underwent three hyperglycaemic clamps (15 mmol/l) with infusion of GLP-1, GIP or saline. Insulin responses were evaluated as the incremental area under the plasma C-peptide curve. Before and after near-normalisation of blood glucose, the C-peptide responses did not differ during the early phase of insulin secretion (0-10 min). The late phase C-peptide response (10-120 min) increased during GIP infusion from 33.0 +/- 8.5 to 103.9 +/- 24.2 (nmol/l) x (110 min)(-1) (p < 0.05) and during GLP-1 infusion from 48.7 +/- 11.8 to 126.6 +/- 32.5 (nmol/l) x (110 min)(-1) (p < 0.05), whereas during saline infusion the late-phase response did not differ before vs after near-normalisation of blood glucose (40.2 +/- 11.2 vs 46.5 +/- 12.7 [nmol/l] x [110 min](-1)). Near-normalisation of blood glucose for 4 weeks improves beta cell responsiveness to both GLP-1 and GIP by a factor of three to four. No effect was found on beta cell responsiveness to glucose alone. CLINICALTRIALS.GOV ID NO.: NCT 00612950. This study was supported by The Novo Nordisk Foundation, The Medical Science Research Foundation for Copenhagen.
            Article 0 comments Cited 123 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes.

              Julio Teixeira, B Oliván, K. Wang … (2007)
              Limited data on patients undergoing Roux-en-Y gastric bypass surgery (RY-GBP) suggest that an improvement in insulin secretion after surgery occurs rapidly and thus may not be wholly accounted for by weight loss. We hypothesized that in obese patients with type 2 diabetes the impaired levels and effect of incretins changed as a consequence of RY-GBP. Incretin (gastric inhibitory peptide [GIP] and glucagon-like peptide-1 [GLP-1]) levels and their effect on insulin secretion were measured before and 1 month after RY-GBP in eight obese women with type 2 diabetes and in seven obese nondiabetic control subjects. The incretin effect was measured as the difference in insulin secretion (area under the curve [AUC]) in response to an oral glucose tolerance test (OGTT) and to an isoglycemic intravenous glucose test. Fasting and stimulated levels of GLP-1 and GIP were not different between control subjects and patients with type 2 diabetes before the surgery. One month after RY-GBP, body weight decreased by 9.2 +/- 7.0 kg, oral glucose-stimulated GLP-1 (AUC) and GIP peak levels increased significantly by 24.3 +/- 7.9 pmol x l(-1) x min(-1) (P < 0.0001) and 131 +/- 85 pg/ml (P = 0.007), respectively. The blunted incretin effect markedly increased from 7.6 +/- 28.7 to 42.5 +/- 11.3 (P = 0.005) after RY-GBP, at which it time was not different from that for the control subjects (53.6 +/- 23.5%, P = 0.284). These data suggest that early after RY-GBP, greater GLP-1 and GIP release could be a potential mediator of improved insulin secretion.
              Article 0 comments Cited 109 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Diabetes
                Journal ID (iso-abbrev): Diabetes
                Journal ID (hwp): diabetes
                Journal ID (pmc): diabetes
                Journal ID (publisher-id): Diabetes
                Title: Diabetes
                Publisher: American Diabetes Association
                ISSN (Print): 0012-1797
                ISSN (Electronic): 1939-327X
                Publication date (Print): September 2013
                Publication date (Electronic): 15 August 2013
                Volume: 62
                Issue: 9
                Pages: 3044-3052
                Affiliations
                [1] 1Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
                [2] 2Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
                [3] 3Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
                [4] 4Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark
                Author notes
                Corresponding author: Nils B. Jørgensen, nils.bruun.joergensen@ 123456regionh.dk .
                Article
                Publisher ID: 0022
                DOI: 10.2337/db13-0022
                PMC ID: 3749359
                PubMed ID: 23649520
                SO-VID: 903e4cf6-7d9a-498d-a710-95405231cbc7
                Copyright © © 2013 by the American Diabetes Association.
                License:

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                Date received : 07 January 2013
                Date accepted : 30 April 2013
                Page count
                Pages: 9
                Categories
                Subject: Original Research
                Subject: Metabolism

                ScienceOpen disciplines: Endocrinology & Diabetes
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes

                Comments

                Comment on this article

                scite_

                Similar content342

                See all similar

                Cited by89

                See all cited by

                Most referenced authors675

                See all reference authors