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Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography

Abstract

Background

In type 2 diabetes mellitus, there is a progressive loss of beta-cell mass. Bariatric surgery has in recent investigations showed promising results in terms of diabetes remission, but little is established regarding the effect of surgery on the survival or regeneration of pancreatic beta-cells. In this study, we aim to explore how bariatric surgery with its subsequent hormonal alterations affects the islets of Langerhans.

Methods

Twenty-four Goto-Kakizaki rats were operated with duodenojejunostomy (DJ), sleeve gastrectomy (SG) or sham operation. From the 38th week after surgery, body weight, fasting blood glucose, glycosylated hemoglobin, mixed meal tolerance with repeated measures of insulin, glucagon-like peptide 1, gastrin and total ghrelin were evaluated. Forty-six weeks after surgery, the animals were euthanized and the total beta-cell mass in all animals was examined by three-dimensional volume quantification by optical projection tomography based on the signal from insulin-specific antibody staining.

Results

Body weight did not differ between groups (P g = 0.37). SG showed lower fasting blood glucose compared to DJ and sham (P g = 0.037); HbA1c levels in SG were lower compared to DJ only (p < 0.05). GLP-1 levels were elevated for DJ compared to SG and sham (P g = 0.001), whereas gastrin levels were higher in SG compared to the two other groups (P g = 0.002). Beta-cell mass was significantly greater in animals operated with SG compared to both DJ and sham (p = 0.036).

Conclusion

Sleeve gastrectomy is superior to duodenojejunostomy and sham operation when comparing the preservation of beta-cell mass 46 weeks after surgery in Goto-Kakizaki rats. This could be related to both the increased gastrin levels and the long-term improvement in glycemic parameters observed after this procedure.

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Acknowledgments

We would like to thank biomedical laboratory scientist (BLS) Britt Schulze for performing gastrin RIA. We also would like to thank BLS Kristin Graven for performing HbA1c and general blood analyses. We would also thank PhD MSc Anna Eriksson for sharing and communicating her knowledge on the OPT protocol. Again we will express our gratitude toward the staff at the Department of comparative medicine at NTNU for technical assistance and their devoted care for all our animals. This study has been supported by the Norwegian University of Science and Technology (NTNU), Centre for Obesity, The Norwegian National Advisory Unit on Advanced Laparoscopic Surgery (NSALK) and The Cancer Fund, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, and The Swedish Research Council, Sweden.

Disclosures

Eivind Grong MS, Ingerid Brænne Arbo BLS PhD, Christoffer Nord MSc, Maria Eriksson MSc, Ulf Ahlgren MSc PhD, Bård Erik Kulseng MD PhD and Ronald Mårvik MD PhD have no conflicts of interest or financial ties to disclose.

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Grong, E., Kulseng, B., Arbo, I.B. et al. Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography. Surg Endosc 30, 532–542 (2016). https://doi.org/10.1007/s00464-015-4236-4

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Keywords

  • Duodenojejunostomy
  • Sleeve gastrectomy
  • Gastrin
  • Glucagon-like peptide 1
  • Beta-cell mass
  • Optical projection tomography
  • Goto-Kakizaki rats
  • Type 2 diabetes mellitus