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Beta-cell sensitivity to insulinotropic gut hormones is reduced after gastric bypass surgery
  1. Marzieh Salehi1,2,3,
  2. Amalia Gastaldelli4,
  3. David A D’Alessio1,5
  1. 1 Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
  2. 2 Department of Medicine, University of Texas at San Antonio, San Antonio, Texas, USA
  3. 3 Bartter Research Unit, South Texas Veterans Health Care System, Audie Murphy Hospital, San Antonio, Texas, USA
  4. 4 Cardiometabolic Risk Unit, CNR Institute of Clinical Physiology, Pisa, Italy
  5. 5 Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
  1. Correspondence to Dr Marzieh Salehi, Division of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio TX 78229, USA; salehi{at}


Objective Postprandial hyperinsulinaemia after Roux-en Y gastric bypass (GB) has been attributed to rapid nutrient flux from the gut, and an enhanced incretin effect. However, it is unclear whether surgery changes islet cell responsiveness to regulatory factors. This study tested the hypothesis that β-cell sensitivity to glucagon like-peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) is attenuated after GB.

Design Ten non-diabetic subjects with GB, and 9 body mass index (BMI)-matched and age-matched non-surgical controls (CN) with normal glucose tolerance had blood glucose clamped at ~7.8 mM on three separate days. Stepwise incremental infusions of GLP-1 (15, 30, 60, 120 and 300 ng/LBkg/h), GIP (75, 150, 300, 600 and 1200 ng/LBkg/h) or saline were administered from 90 to 240 min and insulin secretion measured.

Results GB subjects had similar fasting glucose levels but lower fasting insulin compared with CN, likely due to increased insulin clearance. The average insulin secretion rates (ISRs) to 7.8 mM glucose were ~30% lower in GB relative to CN subjects. However, incretin-stimulated ISRs, adjusted for insulin sensitivity and glucose-stimulated insulin secretion, were even more attenuated in the GB subjects, by threefold to fourfold (AUCISR(90−240 min) during GLP-1 and GIP: 47±8 and 44±12 nmol in GB and 116±16 and 161±44 in CN; p<0.01).

Conclusion After GB, the sensitivity of insulin secretion to both glucose and incretins is diminished.

  • gastric bypass
  • beta-cell sensitivity
  • GLP-1
  • GIP

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  • Contributors MS: designed and supervised the study, obtained the data, analysed and interpreted the data, and wrote the manuscript; as the guarantor takes full responsibility for the work including the study design, access to data, and the decision to submit and publish the manuscript. AG: analysed the data. DAD and AG: contributed to interpretation of data and review/editing of the manuscript.

  • Funding This work was supported by grants from the National Institute of Health, DK105379 (MS), DK083554 (MS), and DK101991 (DD) and in part by National Center for Advancing Translational Sciences, National Institute of Health grant 8 UL1 TR000077.

  • Disclaimer Parts of this study were presented at American Diabetes Association, 74th Scientific Session, Boston, MA.

  • Competing interests None declared.

  • Ethics approval The experimental protocol was approved by the institutional review board of the University of Cincinnati.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent for publication Not required.

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