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Background Bariatric surgery offers successful resolution of type 2 diabetes mellitus (T2DM).However,recurrence of T2DM has been observed in a number of patients with initial resolution after bariatric surgery.This study aimed to induce reversal of the improvement of diabetes in T2DM rats after duodenal-jejunal bypass (DJB),and identify the effects of weight changes and gut hormones that might be involved.Methods DJB surgery was performed in two T2DM rat models (n=20 for each group):non-obese Goto-Kakizaki (GK) rats,and moderately-obese T2DM rats induced by a combination of a high-fat diet (HFD) and low-dose streptozotocin (HS rats).The controls were sham-operated and non-treated rats.All rats were then randomly divided into HFD- and low-fat diet (LFD)-fed groups.Glucose tolerance,insulin tolerance,glucose-stimulated insulin,glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion,food intake and body weight were measured and compared with controls.Results DJB surgery resulted in a significant improvement in glucose tolerance in both GK and HS rats fed with either HFD or LFD.In contrast to LFD-fed rats,improved glucose tolerance was impaired in GK and HS rats fed with an HFD,accompanied by re-impairment of insulin tolerance and failure in enhancement of insulin secretion.There was no significant difference in food intake and body weight between DJB-operated and control rats,and between HFD- and LFD-fed rats.Glucose-stimulated GLP-1 and PYY levels were significantly increased after DJB surgery; however,they were not significantly different between HFD- and LFD-fed rats.Conclusion An HFD reverses the improvement in glucose tolerance induced by DJB surgery in T2DM rats,primarily ascribing to the re-impairment of insulin sensitivity,but does not change body weight,GLP-1 and PYY levels.