The Effect and Mechanism of Duodenal-Jejunal Bypass to Treat Type 2 Diabetes Mellitus in a Rat Model.

OBJECTIVES

Bariatric surgery can treat obesity and T2DM, but the specific mechanism is unknown. This study investigated the effect and possible mechanism of duodenal-jejunal bypass (DJB) to treat T2DM.

METHODS

A T2DM rat model was established using a high-fat, high-sugar diet and a low dose of streptozotocin. DJB surgery and a sham operation (SO) were performed to analyze the effects on glucose homeostasis, lipid metabolism, and inflammation changes. Furthermore, the glucagon-like peptide-1 (GLP-1) in the ileum and the markers of endoplasmic reticulum stress (ERS) in the pancreas were examined after the surgery. The insulinoma cells (INS-1) were divided into three groups; group A was cultured with a normal sugar content (11.1 mmol/L), group B was cultured with fluctuating high glucose (11.1 mmol/L alternating with 33.3 mmol/L), and group C was cultured with fluctuating high glucose and exendin-4 (100 nmol/L). The cells were continuously cultured for 7 days in complete culture medium. The viability of the INS-1 cells was then investigated using the MTT method, apoptosis was detected by flow cytometry, and the ERS markers were detected by Western blot.

RESULTS

The blood glucose, lipids, insulin, and TNF-α were significantly elevated in the T2DM model. A gradual recovery was observed in the DJB group. GLP-1 expression in the distal ileum of the DJB group was significantly higher than that in the T2DM control group (DM) and the SO group (p < 0.05), and the markers of ERS expression in the pancreases of the DJB group decreased significantly more than those of groups DM and SO (p < 0.05). Compared with group A, the cell viability in group B was decreased, and the ERS and apoptosis were increased (p < 0.05). However, compared with group B, the cell viability in group C was improved, and the ERS and apoptosis declined (p < 0.05).

CONCLUSIONS

DJB can be used to treat T2DM in T2DM rats. The mechanism may be that the DJB stimulates the increased expression of GLP-1 on the far side of the ileum, and then, GLP-1 inhibits ERS in the pancreas, reducing the apoptosis of β cells to create a treatment effect in the T2DM rats.