Duodenal-Jejunal Exclusion Surgery Improves Type 2 Diabetes in a Rat Model Through Regulation of Early Glucose Metabolism.

OBJECTIVES: Metabolic surgery has been proven to be widely effective for the control of glucose and weight in patients with type 2 diabetes and obesity. However, the effects of bariatric surgery on nonobesity type 2 diabetes and its metabolism are still unclear. This study aimed to measure the effects of duodenal-jejunal exclusion on glycometabolism in nonobese rats with type 2 diabetes and to investigate its mechanisms. METHODS: Goto-Kakizaki rats and Sprague-Dawley rats were divided into duodenal-jejunal exclusion operation groups and sham operation groups, respectively. The glucose-relative parameters were measured before and after operation. Eight weeks postoperation, the levels of the key regulators of intestinal gluconeogenesis and the crucial proteins of hepatic insulin signalling were evaluated. RESULTS: Postoperatively, the concentrations of blood glucose declined, and the insulin sensitivity increased significantly in rats with diabetes. However, there was no obvious reduction in weight. Eight weeks postoperatively, the mRNA levels of glucose-6-phosphatase and phosphoenolpyruvate pyruvate kinase in the jejunum and the levels of insulin receptor substrate-2 and glucose transporter-2 in the liver were significantly increased compared with the rats that had undergone the sham operation. CONCLUSIONS: Duodenal-jejunal exclusion surgery is an effective procedure for improving glucose metabolism independent of weight loss in nonobese rats with diabetes. The molecular mechanisms might be associated with a series of processes, including intestinal gluconeogenesis and the hepatic insulin signaling pathway.

The antidiabetic effect of jejunal exclusion surgery for T2DM rats / 中华内分泌外科杂志

Objective To study the curative effects of jejunal exclusion surgery for STZ-induced T2DM SD rats.Methods 60 SD rats were induced to be the T2DM SD rats by intraperitoneal injection of streptozotocini.As a result,55 T2DM SD rats were successfully acquired which were randomly divided into 3 groups,20 rats in the jejunal exclusion group (A),20 rats in the sham operation group (B) and 15 rats in the control group (C).Jejunal exclusion surgery was performed in group A,jejunojejunostomy was performed in group B,and group C were fed normally.The body weight,fasting blood glucose,fasting plasma insuhn level and GLP-1 level were measured before operation and at the 1st,2rid,4th,8th and 16th week after operation.Results As compared with that before operation and that of the control group,the body weight in group A markedly declined at the 2nd,4th,8th and 16th week (352.14±9.00,342.84±8.90,336.64±10.26,330.34±9.12,P＜0.05).The fasting plasma glucose levels in group A markedly declined at the 2nd,4th,8th and 16th week (14.62±1.10,12.12±1.38,8.75± 1.06,7.55±1.00,P＜0.05).The fasting plasma insulin level in group A was maikedly increased at the 2nd,4th,8th and 16th week (14.62±3.10,16.12±3.38,17.75±4.06,17.55±3.10,P＜0.05).GLP-1 level in group A was markedly increased at the 1st,2nd,4th,8th and 16th week (11.02±0.85,14.42±1.18,16.02±1.59,17.62±1.02,18.12±0.71,P＜0.05).Conclusions The jejunal exclusion surgery is effective in controlling blood glucose,which is an ideal and lasting method.This surgery has also showed influence on body weight.

Effects of Duodenal-Jejunal Exclusion and New Bilio-Pancreatic Diversion on Blood Glucose in Rats with Type 2 Diabetes Mellitus.

OBJECTIVE: The current study aimed to investigate the effects of duodenal-jejunal bypass (DJB), new bilio-pancreatic diversion (NBPD), and duodenal-jejunal exclusion (DJE) on blood glucose in rats with type 2 diabetes mellitus (T2DM). METHODS: Male Sprague Dawley rats were fed with high glucose, high fat food, and intraperitoneally injected with streptozotocin to establish a T2DM animal model. T2DM rats were randomly assigned into 4 groups: a sham group (n = 8), DJB group (n = 9), NBPD group (n = 10), and DJE group (n = 10). Body weight, 2-h postprandial glucose, oral glucose tolerance, fasting serum bile acid, 2-h postprandial serum bile acid, fasting insulin, 2-h postprandial insulin (INS), fasting glucagon-like peptide-1 (GLP-1), and 2-h postprandial GLP-1 were measured before and after surgery. RESULTS: Six weeks after surgery, the 2-h postprandial glucose in the DJB (16.1 ± 6.7 mmol/L) and NBPD (19.5 ± 5.7 mmol/L) groups decreased significantly compared to the sham group (25.8 ± 4.9 mmol/L) (P < 0.05). There was no significant difference between the DJE (25.0 ± 5.0 mmol/L) and sham groups (P > 0.05). Four weeks after surgery, fasting serum bile acid in the DJB group (60.6 ± 11.4 µmol/L) and NBPD group (54.4 ± 7.64 µmol/L) was significantly higher than that in the sham group (34.3 ± 6.98 µmol/L; P < 0.05). However, fasting GLP-1, 2-h postprandial GLP-1, and insulin remained unchanged at different time points after surgery (P > 0.05). Body weight remained stable after surgery in all 4 groups (P > 0.05). CONCLUSION: NBPD plays a major role in the therapy of T2DM with DJB. NBPD may significantly increase fasting serum bile acid in T2DM rats, an action that may be one of the mechanisms underlying the therapeutic effects of DJB on T2DM.

Duodenal-jejunal exclusion improves insulin resistance in type 2 diabetic rats by upregulating the hepatic insulin signaling pathway.

OBJECTIVES: Previous studies have shown duodenal-jejunal exclusion (DJE) results in the rapid resolution of type 2 diabetes; however, the underlying mechanism is unknown. This study aimed to measure the hepatic expression of insulin receptor substrate-2 (IRS-2) and glucose transporter-2 (GLUT-2) in type 2 diabetic rats post-DJE, and to investigate their roles in improved hepatic insulin resistance and glucose intolerance. METHODS: Type 2 diabetic Sprague-Dawley (SD) rats were randomly divided into DJE operation (DO) and control (DC) groups. Normal SD rats were also divided into DJE operation and control groups. Fasting plasma glucose and insulin concentrations were measured, and the quantitative insulin sensitivity check index (QUICKI) and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) were calculated. Eight weeks postoperation, the hepatic IRS-2 and GLUT-2 protein and mRNA levels were measured using western blotting and reverse transcription polymerase chain reaction, respectively. RESULTS: The fasting blood glucose in the DO group decreased from a preoperative level of 20.21 ± 2.14 mmol/L to 8.50 ± 2.19 mmol/L (P < 0.05) 8 wk post-DJE. A change in the QUICKI revealed a dramatic increase, and HOMA-IR showed a significant decrease in the DO group (P < 0.05). Additionally, the IRS-2 and GLUT-2 protein and mRNA levels at 8 wk postoperation were significantly increased in the DO group compared with the DC group. CONCLUSIONS: DJE led to upregulated hepatic IRS-2 and GLUT-2 expression in the hepatic insulin signaling pathway and improved insulin sensitivity in type 2 diabetic rats.