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The effect of hypergastrinemia following sleeve gastrectomy and pantoprazole on type 2 diabetes mellitus and beta-cell mass in Goto-Kakizaki rats

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Abstract

Purpose

Metabolic surgery alters the secretion of gastrointestinal hormones that influence glycemic control. Elevated gastrin has been suggested to benefit patients with type 2 diabetes and has been reported following sleeve gastrectomy in rats. The present study compares the effect of hypergastrinemia following sleeve gastrectomy with proton-pump inhibitor therapy on glycemic control and beta-cell mass in lean, diabetic animals.

Methods

Thirty-three diabetic Goto-Kakizaki rats were randomized into pantoprazole + sham operation (GK-PPI), sleeve gastrectomy (GK-SG) and vehicle + sham operation (GK-V). Body weight, glucose parameters, HbA1c, glucagon-like peptide 1, gastrin, insulin and lipids were evaluated for eighteen postoperative weeks. Total beta-cell mass was quantified by optical projection tomography.

Results

After surgery, body weight development was equal among groups (P g = 0.75). Fasting and stimulated gastrin increased for GK-PPI and GK-SG vs. GK-V (p < 0.05 for all). Fasting blood glucose was decreased for GK-PPI and GK-SG vs. GK-V (p < 0.05 and p = 0.052). HbA1c was lower for GK-SG vs. GK-V at 6 weeks and for GK-PPI vs. GK-V at twelve- and eighteen weeks postoperative (p < 0.05 for all); a borderline difference was observed for GK-SG vs. GK-V at 18 weeks (p = 0.054). Total- and LDL cholesterol was elevated for GK-PPI compared to the other two groups (p < 0.05 for all). Beta-cell mass did not differ among groups (p = 0.35).

Conclusions

Hypergastrinemia following sleeve gastrectomy and pantoprazole has a similar, modest effect on glycemic control in Goto-Kakizaki rats but does not enhance beta-cell mass after 18 weeks. Hypergastrinemia in the setting of T2DM might be of clinical relevance.

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Acknowledgements

We would like to thank biomedical laboratory scientist (BLS) Anne Eleanor Kristensen for performing gastrin RIA analyses. We also would like to thank BLS Kristin Graven for performing HbA1c and lipid analyses. Finally, we would like to express our gratitude towards 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 Research and Innovation (ObeCe) and The Norwegian National Advisory Unit on Advanced Laparoscopic Surgery (NSALK), St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, Umeå University and The Swedish Research Council, Sweden.

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Authors and Affiliations

  1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Post Box 8905, 7491, Trondheim, Norway

    E. Grong, I. B. Arbo, B. E. Kulseng & R. Mårvik

  2. Umeå Center for Molecular Medicine (UCMM), Umeå University, Umeå, Sweden

    C. Nord, M. Eriksson & U. Ahlgren

  3. Centre for Obesity Research and Innovation (ObeCe), St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

    B. E. Kulseng & R. Mårvik

  4. Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

    B. E. Kulseng

  5. Department of Gastrointestinal Surgery and Norwegian National Advisory Unit on Advanced Laparoscopic Surgery (NSALK), St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

    E. Grong & R. Mårvik

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  1. E. Grong
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Correspondence to E. Grong.

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This experiment was beforehand approved by the Norwegian Animal Research Authority (FOTS 7226). All applicable international, national and institutional guidelines for the care and use of animals were followed.

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Authors have no conflicts of interest or financial ties to disclose.

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Grong, E., Nord, C., Arbo, I.B. et al. The effect of hypergastrinemia following sleeve gastrectomy and pantoprazole on type 2 diabetes mellitus and beta-cell mass in Goto-Kakizaki rats. J Endocrinol Invest 41, 691–701 (2018). https://doi.org/10.1007/s40618-017-0793-9

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