Original article
Duodenal-jejunal bypass attenuates progressive failure of pancreatic islets in streptozotocin-induced diabetic rats

https://doi.org/10.1016/j.soard.2016.08.500Get rights and content

Abstract

Background

Preservation of pancreatic beta cell function has been increasingly appealing in the treatment of type 2 diabetes. Evidence is still limited on how bariatric surgery affects pancreatic beta cell apoptosis.

Setting

University medical center.

Objective

The study aimed to investigate the effect of a major component of Roux-en-Y gastric bypass, duodenal-jejunal bypass, on protecting pancreatic beta cells from progressive loss.

Methods

Forty-five normal Sprague–Dawley rats were randomly assigned into 3 groups: duodenal-jejunal bypass (DJB) group (n = 16) and sham (S) group (n = 17), based upon the procedure received, and a control (C) group (n = 12) without any procedure performed, to eliminate potential traumatic effects from surgery. Ten days after surgery, streptozotocin (STZ, 45 mg/kg weight) was injected intraperitoneally into each animal, including the control animals, to selectively induce pancreatic beta cell apoptosis. Weight, food intake, plasma glucose level, and the results of an oral glucose tolerance test were measured before surgery, pre-STZ injection, and up to 4 weeks after STZ injection. Plasma insulin and glucagon-like peptide-1 levels were also assayed during oral glucose tolerance test. At the end, pancreatic tissues were sliced and stained for beta cell analysis.

Results

There were no significant differences in weight among all groups at any time points measured, despite rats in the S and C groups consuming more food than those in the DJB group as measured on day 10 (P<.05) and day 20 (P<.01) after STZ injection. Animals undergoing DJB did not experience symptoms typical of uncompensated diabetes, including hyperphagia and progressive weight loss. After STZ injection, fasting plasma glucose levels in the DJB group were significantly lower than those in the C and S groups (P<.001). When challenged by glucose load, DJB rats also had a better glycemic excursion (P<.01) and incretin response compared with C and S rats (P<.05). In addition, pancreatic beta cell size and mass was better preserved in DJB rats (P< .001).

Conclusion

DJB is able to protect pancreatic beta cells from apoptosis, which leads to better glycemic control and delayed onset of diabetes. These results imply the necessity of including a DJB component when designing bariatric procedure to achieve a better long-term outcome.

Section snippets

Animals

A cohort of 8-week old male Sprague–Dawley (SD) rats weighing 180–200 g was adopted from the Shanghai Laboratory Animal Research Center (Shanghai, China). The rats were housed in individual cages with controlled temperature (24±2°C), humidity (40%–70%), and light/dark cycle (12 hr light/12 hr dark, with light on at 7:00 a.m.) and allowed unrestricted access to standard rat chow and tap water. The study protocol was reviewed and approved by the Institutional Animal Care and Utilization Committee

Food intake and weight

Food intake and weight of each rat were measured 1 day before and 1 week after the DJB or sham procedure, and 10 and 20 days after STZ administration. At the onset of this experiment, animals were randomized into 3 groups, all of which had a comparable baseline in food intake and weight. Then the DJB or sham procedure was performed to induce hormonal and cytokine changes in rats. One week after surgery, there was no significant difference in food intake among DJB, S, and C groups.

Ten days after

Discussion

In this study, nonobese healthy rats underwent prophylactic DJB to reroute the intestine to induce beneficial biological or hormonal effects. Both rats that had a sham procedure and rats that did not have surgery served as controls. A moderate dosage of STZ then was administered to selectively induce pancreatic beta cell apoptosis in all the rats. After these treatments, we found that the rats that underwent DJB did not experience typical symptoms of uncompensated diabetes, including

Disclosures

The authors have no commercial associations that might be a conflict of interest in relation to this article.

Acknowledgments

The authors wish to thank Zhengdong Qiao, Yueqian Wang, Lili Gao, and Yongjun Liang for assistance with the experiments and technical support and Dan Yang for valuable discussions. This study was supported by Young Medical Talents Training Program of Pudong Health Bureau of Shanghai (Grant No. PWRq2013-14), Shanghai Pujiang Telant Project Grant (No. 14 PJ1407800), Shanghai Commission of Science and Technology Grant (Grant No.124119 b1800), as well as Pudong Bureau of Health and Family Planning

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