Effects of duodenal-jejunal bypass on structure of diaphragm in western diet obese rats

Abstract Purpose: To evaluate the effects of duodenal-jejunal bypass (DJB) on the diaphragm muscle of obese rats fed on a western diet (WD) . Methods: Eighteen male Wistar rats were fed a standard rodent chow diet (CTL group) or WD ad libitum. After 10 weeks, WD rats were submitted to sham (WD SHAM) or duodenal-jejunal bypass (WD DJB). The structure, ultrastructure, collagen content and the morphometry of the neuromuscular junctions (NMJs) were analyzed two months after surgery. Results: WD SHAM rats displayed an increase in body weight, the Lee index and retroperitoneal and peri-epididymal fat pads compared to the CTL group. DJB did not alter these parameters. The muscle fiber structure and NMJs were similar in the WD SHAM and CTL groups. However, the WD SHAM group showed alterations in the fiber ultrastructure, such as loosely arranged myofibrils and Z line disorganization. In addition, WD SHAM animals presented a considerable amount of lipid droplets and a reduction in the percentage of collagen compared to the CTL group. DJB did not affect the structure or ultrastructure of the muscle fibers or the NMJs in the diaphragm of the WD DJB animals. Conclusion: Duodenal-jejunal bypass did not improve the alterations observed in the diaphragm of western diet obese-rats.

Improvement effect of duodenal-jejunal bypass on inflammatory status of biliopancreatic limb of ZDF rats and its mechanism / 吉林大学学报(医学版)

Objective:To investigate the improvement effects of duodenal-jejunal bypass (DJB)on the blood glucose homeostasis,insulin resistance and inflammation of the obese type 2 diabetic (T2DM)ZDF rats,and to discuss its possible mechanism.Methods:A total of 20 ZDF rats were randomly divided into DJB operation group and sham operation group (n = 10).There were 8 rats survived in each group after operation.The level of blood glucose (FBG)was detected by Roche glucose meter at 1 week before operation,2 weeks,4 weeks and 6 weeks after operation;the fasting serum insulin level of the rats was measured by ELISA kit;the insulin sensitivity index (HOMA-ISI)and insulin resistance index (HOMA-IR)were calculated.The rats were executed 6 weeks after operation.HE staining was used to observe the morphology of the inflammatory cells in BP limb of the rats;the expression levels of AMPK and pAMPK in BP lamb of the rats were observed by immunohistochemical staining;the expression levels of interleukin 1β(IL-1β),interleukin 6 (IL-6),tumor necrosis factorα(TNF-α),nuclear factorκB (NF-κB),and interleukin 10 (IL-10)mRNA of the rats were detected by QRT-PCR method.Results:From the 2nd week after operation,compared with before operation,the FBG levels of the rats in DJB operation group were decreased (t=3.798,P <0.05);compared with sham operation group,the FBG level of the rats in DJB operation group was decreased (t=3.205,P <0.05).Six weeks after operation,compared with sham operation group,the HOMA-IR of the rats in DJB operation group was significantly decreased (t=4.441,P <0.05)and the HOMA-ISI was significantly increased (t=-8.65,P < 0.05).The HE staining results showed that compared with sham operation group,the morphology of the inflammatory cells in BP limb of the rats in DJB operation group was significantly improved.The QRT-PCR results showed that the expression levels of IL-1β,IL-6,TNF-αand NF-κB of the rats in DJB operation group was significantly decreased compared with sham operation group (P < 0.05), while the expression level of IL-10 was significantly increased (P < 0.05).The immunohistochemical test results showed that the expression levels of AMPK and pAMPK in BP lamb of the rats in DJB operation group were increased compared with sham operation group.Conclusion:DJB can significantly improve the blood glucose homeostasis and insulin resistance in the T2DM rats,and its mechanism may be related to the decreased expressions of inflammatory factors and the activation of AMPK molecules in BP lamb of the T2DM rats.

Duodenal-jejunal bypass normalizes pancreatic islet proliferation rate and function but not hepatic steatosis in hypothalamic obese rats

Modifications in life-style and/or pharmacotherapies contribute to weight loss and ameliorate the metabolic profile of diet-induced obese humans and rodents. Since these strategies fail to treat hypothalamic obesity, we have assessed the possible mechanisms by which duodenal-jejunal bypass (DJB) surgery regulates hepatic lipid metabolism and the morphophysiology of pancreatic islets, in hypothalamic obese (HyO) rats. During the first 5 days of life, male Wistar rats received subcutaneous injections of monosodium glutamate (4 g/kg body weight, HyO group), or saline (CTL). At 90 days of age, HyO rats were randomly subjected to DJB (HyO DJB group) or sham surgery (HyO Sham group). HyO Sham rats were morbidly obese, insulin resistant, hypertriglyceridemic and displayed higher serum concentrations of non-esterified fatty acids (NEFA) and hepatic triglyceride (TG). These effects were associated with higher expressions of the lipogenic genes and fatty acid synthase (FASN) protein content in the liver. Furthermore, hepatic genes involved in β-oxidation and TG export were down-regulated in HyO rats. In addition, these rats exhibited hyperinsulinemia, β-cell hypersecretion, a higher percentage of islets and β-cell area/pancreas section, and enhanced nuclear content of Ki67 protein in islet-cells. At 2 months after DJB surgery, serum concentrations of TG and NEFA, but not hepatic TG accumulation and gene and protein expressions, were normalized in HyO rats. Insulin release and Ki67 positive cells were also normalized in HyO DJB islets. In conclusion, DJB decreased islet-cell proliferation, normalized insulinemia, and ameliorated insulin sensitivity and plasma lipid profile, independently of changes in hepatic metabolism.

Laparoscopic sleeve gastrectomy with duodenal-jejunal bypass for the treatment of type 2 diabetes mellitus / 中华消化外科杂志

Objective To investigate the clinical effects of laparoscopic sleeve gastrectomy with duodenaljejunal bypass (LSG + DJB) for the treatment of type 2 diabetes mellitus.Methods The clinical data of 17 patients with type 2 diabetes mellitus who underwent LSG + DJB at the Xijing Hospital of the Fourth Military Medical University from March 2013 to February 2014 were retrospectively analyzed.The fasting blood glucose,postprandial 2-hour blood glucose,glycosylated hemoglobin (HbA1c) and body mass index (BMI) in 17 patients before operation were (9.2 ± 0.6) mmol/L,(14.4 ± 2.2) mmol/L,8.3％ ± 1.2％ and (29.4 ± 2.2) kg/m2,respectively.All the patients received LSG + DJB and were followed up by outpatient examination up to March 2015.The pre-and post-operative 12-month fasting blood glucose,postprandial 2-hour blood glucose,HbA1 c and BMI in 17 patients were compared.Measurement data with normal distribution were presented as-x ± s and analyzed by the t test.Results All the 17 patients received successful laparoscopic LSG + DJB without conversion to open surgery.The operation time,volume of intraoperative blood loss and recovery time of postoperative gastrointestinal function were (141 ±53)minutes,40 mL and 2.5 days.Of 3 patients with postoperative complications,1 patient with anastomotic leakage at postoperative day 5 received reoperation by laparoscopic Roux-en-Y gastric bypass,1 patient with digestive tract obstruction at postoperative day 10 released obstruction by reoperation and 1 patient with left subphrenic abscess and leakage at the upper of the stomach at postoperative week 2 was cured by the symptomatic treatment.The duration of hospital stay was 5.2 days.All the patients were followed up for a median time of 16 months (range,13-24 months).The postoperative 12-month fasting blood glucose,postprandial 2-hour blood glucose,HbA1c and BMI in 17 patients were (5.5 ± 0.7)mmol/L,(8.8 ± 1.7)mmol/L,5.1％ ± 0.7％ and (24.7 ± 2.3)kg/m2,which were significantly different from preoperative indicators (t =19.96,10.52,12.06,31.99,P ＜ 0.05).During the follow-up,no anastomotic ulcer and stenosis,dumping syndrome and severe malnutrition were occurred.Conclusion LSG + DJB is safe and feasible for the treatment of type 2 diabetes mellitus,with a good short-term hypoglycemic effect.

Amelioration effect of duodenal-jejunal bypass surgery on insulin-resistance in Goto-Kakizaki rats / 中国实验动物学报

Objective To establish a Goto-Kakizaki ( GK) rat model of duodenal-jejunal bypass( DJB) and ob-serve the changes in insulin-resistance after surgery, and to explore the mechanism of DJB surgery in treatment of type 2 di-abetes mellitus.Methods Male Goto-kakizaki diabetic rats(GK,n=36)were used as experiment group and 18 healthy male Wistar rats as blank group.GK rats were randomly divided into two groups: diabetic control group and DJB surgery group ( n=18) .Euglycemic-hyperinsulinemic clamp technique was performed in 6 rats randomly taken from each group at third week, sixth week and ninth week after surgery, respectively.The expression levels of Gck, G6P, PEPCK mRNA in the liver and GLUT4 content on skeletal muscle cell plasma membrance were detected one week after the clamp test. Results In the DJB surgery group at the end of third week and sixth week after surgery, the levels of glucose infusion rates and the expression levels of Gck, G6P, PEPCK mRNA in the liver showed no statistically significant difference as com-pared with the diabetic control group (P>0.05).In the DJB surgery group at the end of 9th week after surgery, the glu-cose infusion rate and expression level of Gck mRNA in the liver were significantly higher, and the expression of G6P and PEPCK mRNA was significantly lower than those in the diabetic control group ( P0.05 for all) .Conclusions Our results indicate that the mechanism of DJB surgery improving blood glucose level may be closely related to the amel-ioration of insulin-resistance in the liver, thereby augmenting glucose uptake and inhibiting gluconeogenesis in liver through the regulation of glucose metabolism-related enzymes.There is no significant improvement in insulin-resistance in the skele-tal muscles during the experiment period.This result implies that the effect of DJB surgery on type 2 diabetes is related to the duration of therapy.

The effect of duodenal-jejunal bypass on the expression of ileum proglucagon mRNA in Goto-Kakizaki type 2 diabetic rats / 中华内分泌外科杂志

Objective To investigate the effect of duodenal-jejunal bypass(DJB) on glucose metabolism and the expression of ileum proglucagon mRNA in Goto-Kakizaki (GK) type 2 diabetic rats.Methods 18 male GK rats and 1 8 male Wistar rats were randomly divided into 4 groups:GK operation group(group A),GK sham operation group(group B),Wistar operation group (group C),Wistar sham operation group (group D).There were 9 rats in each group.The fasting blood glucose and GLP-1 levels were measured before and at the 8th weekafter surgery.Oral glucose tolerance test was measured,and the area under blood glucose concentration curve wascalculated.Ileum tissues were obtained 8 weeks postoperatively and reverse transcriptase polymerase chain reac-tion was used to detect ileum PG mRNA expression after the operation.Results At the 8th week after surgery,the fasting blood glucose of group A decreased from(8.73 ± 1.30) mmol/L to(5.86 ±0.57) mmol/L(P ＜0.05).Area under blood glucose concentration curve decreased from preoperative(60.23 ± 5.14)mmol · h/L to (47.80 ±1.79) mmol· h/L(P ＜ 0.05).Fasting serum GLP-1 in group A increased from (7.69 ± 0.74) pmol/L to (29.00 ±4.85) pmol/L while postprandial GLP-1 increased from(15.74 ± 5.71) pmol/L to (45.78 ± 7.26) pmol/L (P ＜0.05).At the 8th week after surgery,the ileum PG mRNA level in group A was significantly higher than that in group B(P ＜ 0.05).Conclusions DJB can directly improve glucose metabolism in non-obese type 2 diabetic rats,and the operation has no hypoglycemic effect on normal blood glucose.The increased expression of ileum PG mRNA might contribute to the hypoglycemic effect of the surgery.