Metabolic effects of duodenojejunal bypass surgery in a rat model of type 1 diabetes

Abstract

Background

Metabolic surgery has beneficial metabolic effects, including remission of type 2 diabetes. We hypothesized that duodenojejunal bypass (DJB) surgery can protect against development of type 1 diabetes (T1D) by enhancing regulation of cellular and molecular pathways that control glucose homeostasis.

Methods

BBDP/Wor rats, which are prone to develop spontaneous autoimmune T1D, underwent loop DJB (n = 15) or sham (n = 15) surgery at a median age of 41 days, before development of diabetes. At T1D diagnosis, a subcutaneous insulin pellet was implanted, oral glucose tolerance test was performed 21 days later, and tissues were collected 25 days after onset of T1D. Pancreas and liver tissues were assessed by histology and RT-qPCR. Fecal microbiota composition was analyzed by 16S V4 sequencing.

Results

Postoperatively, DJB rats weighed less than sham rats (287.8 vs 329.9 g, P = 0.04). In both groups, 14 of 15 rats developed T1D, at similar age of onset (87 days in DJB vs 81 days in sham, P = 0.17). There was no difference in oral glucose tolerance, fasting and stimulated plasma insulin and c-peptide levels, and immunohistochemical analysis of insulin-positive cells in the pancreas. DJB rats needed 1.3 ± 0.4 insulin implants vs 1.9 ± 0.5 in sham rats (P = 0.002). Fasting and glucose stimulated glucagon-like peptide 1 (GLP-1) secretion was elevated after DJB surgery. DJB rats had reduced markers of metabolic stress in liver. After DJB, the fecal microbiome changed significantly, including increases in Akkermansia and Ruminococcus, while the changes were minimal in sham rats.

Conclusion

DJB does not protect against autoimmune T1D in BBDP/Wor rats, but reduces the need for exogenous insulin and facilitates other metabolic benefits including weight loss, increased GLP-1 secretion, reduced hepatic stress, and altered gut microbiome.

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Acknowledgements

This study was primarily supported by the SAGES General Research Grant, and in part by grants from the National Institutes of Health including R01 HL122283 (J.M.B.), R01 DK120679 (J.M.B.), P50 AA024333 (J.M.B), and P01 HL147823 (J.M.B.). R.V. was supported by a fellowship of the Fulbright Commission Belgium and a fellowship of the Belgian American Educational Foundation.

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Correspondence to Ali Aminian.

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Dr Philip R. Schauer reported receiving grants from Medtronic, Ethicon, and Pacira and receiving personal fees from Medtronic, GI Dynamics, WL Gore and Associates, Becton Dickinson Surgical, and Global Academy for Medical Education. Dr Stacy A. Brethauer reported receiving grants from Medtronic and GI Windows. Dr Ali Aminian reported receiving grants from Medtronic. Drs Roman Vangoitsenhoven, Rickesha Wilson, Gautam Sharma, Suriya Punchai, Ricard Corcelles, Dvir Froylich, Anny Mulya, John P. Kirwan, Naseer Sangwan, and J. Mark Brown have no conflicts of interest or financial ties to disclose.

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Vangoitsenhoven, R., Wilson, R., Sharma, G. et al. Metabolic effects of duodenojejunal bypass surgery in a rat model of type 1 diabetes. Surg Endosc (2020). https://doi.org/10.1007/s00464-020-07741-y

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Keywords

  • Metabolic surgery
  • Duodenojejunal bypass
  • Diabetes
  • Type 1
  • Insulin
  • Weight loss
  • Microbiome