Effects of duodeno-jejunal bypass on glucose metabolism in obese rats with type 2 diabetes
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To evaluate the foregut and hindgut hypotheses for metabolic surgery in obese rats with diabetes.
Otsuka Long-Evans Tokushima fatty rats were divided into a sham operation group, a partial duodeno-jejunal bypass (P-DJB) group, and a complete DJB (C-DJB) group. P-DJB is a model to test foregut hypothesis, whereas C-DJB is a model to test both hypotheses. We performed oral glucose tolerance tests (OGTT) on all groups at baseline, and then 4 and 8 weeks postoperatively. The rats were killed thereafter and the plasma levels of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were measured. A separate sub-group of C-DJB rats underwent OGTT after treatment with the GLP-1 antagonist, the PYY antagonist, or saline.
Marked improvement of the blood glucose control during the OGTT was noted 8 weeks after C-DJB, but not 8 weeks after P-DJB or the sham operation. The serum GLP-1 and PYY levels were higher in the C-DJB group than in the other two groups. Pretreatment with the GLP-1 antagonist increased the blood glucose levels 30 min after the OGTT in the C-DJB rats.
Improvement in glucose metabolism after DJB was associated with the inflow of bile and pancreatic juice into the ileum, supporting validity of the hindgut hypothesis. GLP-1 appears to play a role in this improvement.
KeywordsDuodeno-jejunal bypass Glucagon-like peptide-1 Peptide YY
We thank Dr. Kazuya Kawano from the Tokushima Research Institute, Otsuka Pharmaceutical Co., Tokushima, Japan for the generous gift of the OLETF rats; Ms. Emiko Shibuya for her technical assistance; and Dr. Michael G. Sarr, Department of Surgery, Mayo Clinic, Minnesota, USA, for reviewing this manuscript. This study was supported by a Grant-In-Aid from the Japanese Society for Parenteral and Enteral Nutrition (2009).
Conflict of interest
Hirofumi Imoto and his co-authors have no potential conflicts of interest or financial interest to disclose.
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