Mingwei Zhong

Effects of sleeve gastrectomy with jejuno-jejunal or jejuno-ileal loop on glycolipid metabolism in diabetic rats

AIM To explore the effect of sleeve gastrectomy (SG) with jejuno-jejunal or jejuno-ileal loop on glycolipid metabolism in diabetic rats. METHODS Diabetic rats, which were induced by high-fat diet (HFD), nicotinamide and low-dose streptozotocin, underwent sham operations, SG, SG with jejuno-ileal loop (SG-JI) and SG with jejuno-jejunal loop (SG-JJ) followed by postoperative HFD. Then, at the time points of baseline and 2, 12 and 24 wk postoperatively, we determined and compared several variables, including the area under the curve for the results of oral glucose tolerance test (AUCOGTT), serum levels of triglyceride, cholesterol and ghrelin in fasting state, homeostasis model assessment of insulin resistance (HOMA-IR), body weight, calorie intake, glucagon-like peptide (GLP)-1 and insulin secretions after glucose gavage at dose of 1 g/kg. RESULTS At 2 wk postoperatively, rats that underwent SG, SG-JJ and SG-JI, compared with sham-operated (SHAM) rats, demonstrated lower body weight, calorie intake and ghrelin (P < 0.05 vs SHAM), enhanced secretion of insulin and GLP-1 after glucose gavage (P < 0.05 vs SHAM), improved AUCOGTT, HOMA-IR, fasting serum triglyceride and cholesterol (AUCOGTT: 1616.9 ± 83.2, 837.4 ± 83.7, 874.9 ± 97.2 and 812.6 ± 81.9, P < 0.05 vs SHAM; HOMA-IR: 4.31 ± 0.54, 2.94 ± 0.22, 3.17 ± 0.37 and 3.41 ± 0.22, P < 0.05 vs SHAM; Triglyceride: 2.35 ± 0.17, 1.87 ± 0.23, 1.98 ± 0.30 and 2.04 ± 0.21 mmol/L, P < 0.05 vs SHAM; Cholesterol: 1.84 ± 0.21, 1.53 ± 0.20, 1.52 ± 0.20 and 1.46 ± 0.23 mmol/L). At 12 wk postoperatively, rats receiving SG-JJ and SG-JI had lower body weight, reduced levels of triglyceride and cholesterol and elevated level of GLP-1 compared to those receiving SG (P < 0.05 vs SG). At 24 wk after surgery, compared with SG, the advantage of SG-JJ and SG-JI for glucolipid metabolism was still evident (P < 0.05 vs SG). SG-JI had a better performance in lipid metabolism and GLP-1 secretion of rats than did SG-JJ. CONCLUSION SG combined with intestinal loop induces better glycolipid metabolism than simple SG, with the lipid metabolism being more improved with SG-JI compared to SG-JJ.

Comparative Effects of Bile Diversion and Duodenal-Jejunal Bypass on Glucose and Lipid Metabolism in Male Diabetic Rats

BackgroundDuodenal-jejunal bypass (DJB) induces rapid and durable improvement in glucose and lipid metabolism. Besides bypassing the proximal gut, DJB also diverts bile acids (BAs) into the distal gut, increasing luminal and systemic BAs that are essential to metabolic homeostasis. The aim of this study is to evaluate whether bile diversion (BD) alone can recapitulate the effects of DJB on glucose and lipid metabolism.MethodsBD, DJB and SHAM procedures were performed in a diabetic rat model induced by high-fat diet (HFD)/streptozotocin (STZ). Body weight, energy intake, blood glucose, serum hormones, insulin sensitivity, lipid profiles, and luminal and systemic BAs were measured postsurgery.ResultsBD reduced body weight, independently of energy intake, whereas DJB had no effects. Luminal and serum BAs were increased after both DJB and BD, and were higher after BD than DJB. During glucose tolerance test, both fasting and postprandial blood glucose concentrations were reduced with DJB and BD, and were lower after DJB than BD. Insulin sensitivity was improved after DJB, but remained unchanged after BD. Fasting and postprandial GLP-1 were equally increased after DJB and BD. Serum triglyceride and free fatty acids were decreased more after BD than DJB, while hepatic triglyceride storage was reduced more after DJB.ConclusionThese observations indicate that BD, which increases luminal and systemic BAs and postprandial GLP-1, represents an important component of DJB in restoring glucose and lipid homeostasis in diabetic state. However, other mechanisms associated with DJB also appear to make complementary contributions to metabolic regulation.

Jejunum-ileum circuit procedure improves glucose metabolism in diabetic rats independent of weight loss.

To introduce a lower‐risk novel surgical procedure to achieve diabetes reversal along with associated hormonal changes.

Bariatric Surgery Ameliorates Diabetic Cardiac Dysfunction by Inhibiting ER Stress in a Diabetic Rat Model

BackgroundCardiac dysfunction is a severe complication of diabetes, with no effective treatment. Currently, bariatric surgery is more and more widely used to attenuate diabetes-associated diseases. The mechanism is not clear. Endoplasmic reticulum (ER) stress-dependent apoptosis has been observed in the progression of diabetic myocardium damage. Therefore, this research was designed to investigate the effects of different bariatric procedures on cardiac dysfunction via ER stress-induced cardiomyocyte apoptosis pathway in a diabetic rat model.MethodsDuodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham surgery were performed in diabetic rats. Echocardiographic examination, H&E staining, Masson staining, and TUNEL staining were performed to measure the diabetes-caused heart damages. ER stress-associated signaling molecules like glucose-regulated protein 78 (GRP78), protein kinase RNA (PKR)-like ER protein kinase (PERK), p-PERK, inositol-requiring enzyme 1ɑ (IRE1ɑ), p-IRE1ɑ, activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), and caspase 12 were measured and compared among DJB group, SG group, and sham group.ResultsCompared with sham group, DJB and SG groups both had significantly lower GRP78, PERK, p-PERK, CHOP, and caspase 12, though there was no statistical change on IRE1ɑ, p-IRE1ɑ, and ATF6. DJB and SG groups also showed improved heart function and lower cardiomyocyte apoptosis in diabetic rats.ConclusionDJB and SG ameliorated cardiac dysfunction by inhibiting PERK-mediated pathway. And no difference was observed on the effects of DJB and SG on ER stress-dependent myocardium damage in diabetic rats.

Alterations in gut microbiota during remission and recurrence of diabetes after duodenal-jejunal bypass in rats

AIM To observe the alterations in gut microbiota in high-fat diet (HFD)-induced diabetes recurrence after duodenal-jejunal bypass (DJB) in rats. METHODS We assigned HDF- and low-dose streptozotocin-induced diabetic rats into two major groups to receive DJB and sham operation respectively. When the DJB was completed, we used HFD to induce diabetes recurrence. Then, we grouped the DJB-operated rats by blood glucose level into the DJB-remission (DJB-RM) group and the DJB-recurrence (DJB-RC) group. At a sequence of time points after operations, we compared calorie content in the food intake (calorie intake), oral glucose tolerance test, homeostasis model assessment of insulin resistance (HOMA-IR), concentrations of glucagon-like peptide 1 (GLP-1), serum insulin, total bile acids (TBAs) and lipopolysaccharide (LPS) and alterations in colonic microbiota. RESULTS The relative abundance of Firmicutes in the control (58.06% ± 11.12%; P < 0.05 vs sham; P < 0.05 vs DJB-RC) and DJB-RM (55.58% ± 6.16%; P < 0.05 vs sham; P < 0.05 vs DJB-RC) groups was higher than that in the sham (29.04% ± 1.36%) and DJB-RC (27.44% ± 2.17%) groups; but the relative abundance of Bacteroidetes was lower (control group: 33.46% ± 10.52%, P < 0.05 vs sham 46.88% ± 2.34%, P < 0.05 vs DJB-RC 47.41% ± 5.67%. DJB-RM group: 34.63% ± 3.37%, P < 0.05 vs sham; P < 0.05 vs DJB-RC). Escherichia coli was higher in the sham (15.72% ± 1.67%, P < 0.05 vs control, P < 0.05 vs DJB-RM) and DJB-RC (16.42% ± 3.00%; P < 0.05 vs control; P < 0.05 vs DJB-RM) groups than in the control (3.58% ± 3.67%) and DJB-RM (4.15% ± 2.76%) groups. Improved HOMA-IR (2.82 ± 0.73, P < 0.05 vs DJB-RC 4.23 ± 0.72), increased TBAs (27803.17 ± 4673.42 ng/mL; P < 0.05 vs DJB-RC 18744.00 ± 3047.26 ng/mL) and decreased LPS (0.12 ± 0.04 ng/mL, P < 0.05 vs DJB-RC 0.19 ± 0.03 ng/mL) were observed the in DJB-RM group; however, these improvements were reversed in the DJB-RC group, with the exception of GLP-1 (DJB-RM vs DJB-RC P > 0.05). CONCLUSION Alterations in gut microbiota may be responsible for the diabetes remission and recurrence after DJB, possibly by influencing serum LPS and TBAs.

Duodenal-Jejunal Bypass Surgery Ameliorates Glucose Homeostasis and Reduces Endoplasmic Reticulum Stress in the Liver Tissue in a Diabetic Rat Model.

BackgroundDuodenal-jejunal bypass (DJB) has been shown to be an effective surgical treatment for type 2 diabetes mellitus (T2DM). However, the underlying mechanisms are poorly understood. Recently, accumulating evidences suggest that endoplasmic reticulum (ER) stress plays an important role in the development of insulin resistance in T2DM. The present study was designed to investigate the effect of DJB on glucose homeostasis, the ER stress state in the liver tissue, and the involving signaling independently of weight loss.MethodsThirty adult male T2DM Sprague-Dawley (SD) rats induced by high-fat diet and low dose of streptozotocin (STZ) were randomly divided into DJB and sham groups. Ten age-matched male SD rats were assigned as the control group. The parameters of body weight and calorie intake were measured at indicated time points. The glucose tolerance and insulin resistance were detected to evaluate the glucose homeostasis. Serum insulin was determined by enzyme-linked immunosorbent assay (ELISA). The markers of ER stress, the activity of c-Jun N-terminal kinase (JNK) and serine phosphorylation of insulin receptor substrate 1 (IRS-1) in the liver tissue, were determined by Western blotting.ResultsDJB induced significant improvements in glucose homeostasis and insulin sensitivity, but without weight loss. DJB improved the ER stress state indicated by decreased protein kinase RNA (PKR)-like ER protein kinase (PERK) and inositol-requiring enzyme 1 (IRE-1) phosphorylation in the liver tissue. The JNK activity and serine phosphorylation of IRS-1 in the liver tissue were significantly reduced after DJB.ConclusionsDJB ameliorates glucose homeostasis. Meanwhile, our study helps to reveal that the reduced hepatic ER stress and the decreased JNK activity may contribute to the improved glucose homeostasis after DJB.

Effects of sleeve gastrectomy plus trunk vagotomy compared with sleeve gastrectomy on glucose metabolism in diabetic rats

AIM To investigate the effects of sleeve gastrectomy plus trunk vagotomy (SGTV) compared with sleeve gastrectomy (SG) in a diabetic rat model. METHODS SGTV, SG, TV and Sham operations were performed on rats with diabetes induced by high-fat diet and streptozotocin. Body weight, food intake, oral glucose tolerance test, homeostasis model assessment of insulin resistance (HOMA-IR), hepatic insulin signaling (IR, IRS1, IRS2, PI3K and AKT), oral glucose stimulated insulin secretion, GLP-1 and ghrelin were compared at various postoperative times. RESULTS Both SG and SGTV resulted in better glucose tolerance, lower HOMA-IR, up-regulated hepatic insulin signaling, higher levels of oral glucose-stimulated insulin secretion, higher postprandial GLP-1 and lower fasting ghrelin levels than the TV and Sham groups. No significant differences were observed between the SG and SGTV groups. In addition, no significant differences were found between the TV and Sham groups in terms of glucose tolerance, HOMA-IR, hepatic insulin signaling, oral glucose-stimulated insulin secretion, postprandial GLP-1 and fasting ghrelin levels. No differences in body weight and food intake were noted between the four groups. CONCLUSION SGTV is feasible for diabetes control and is independent of weight loss. However, SGTV did not result in a better improvement in diabetes than SG alone.

Predictors of glycemic control after sleeve gastrectomy versus Roux-en-Y gastric bypass: a meta-analysis, meta-regression and systematic review

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most commonly performed bariatric procedures globally. However, it remains controversial which procedure provides better glycemic control. To identify predictors of glycemic control after SG versus RYGB, a systematic search of PubMed, EMBASE, and the Cochrane Library was conducted up to January 2017 for comparative studies with both SG and RYGB arms for the treatment of type 2 diabetes (T2D). A meta-analysis and systematic review was performed to evaluate glycemic control after SG versus RYGB with both short- and long-term follow-up. A meta-regression was performed to evaluate impacts of clinical indicators on glycemic control after SG versus RYGB. A total of 17 comparative studies involving 1160 patients were included. SG and RYGB achieved similar diabetic remission rates with both short- and long-term follow-up. However, SG provided lower endpoint glycosylated hemoglobin (A1C) after 1-year follow-up (mean deviation = .17, 95% confidence interval .03-.31, P = .02). When adjusted by baseline A1C, SG and RYGB provided similar percent delta A1C with 1-, 2-, 3-, and 5-year follow-up. The baseline body mass index, duration of T2D, preoperative fasting plasma glucose, and preoperative A1C had predictive value for glycemic control after SG, but only duration of T2D and preoperative A1C were correlated with that after RYGB. These findings showed that the choice of procedure between SG and RYGB predicts no better glycemic control. However, more factors should be considered when SG is recommended to a given patient with diabetes.

Deactivation of the NLRP3 inflammasome in infiltrating macrophages by duodenal-jejunal bypass surgery mediates improvement of beta cell function in type 2 diabetes

OBJECTIVE Bariatric surgery could improve pancreatic beta cell function, thereby leading to the remission of the type 2 diabetes mellitus (T2DM). However, the specific mechanism underlying this phenomenon is yet to be revealed. The aim of this study is to test the hypothesis that Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in infiltrating macrophages plays an important role in the modulation of beta cell function after duodenal-jejunal bypass (DJB) surgery. METHODS DJB and sham surgery were performed in diabetic Sprague-Dawley (SD) rats induced by high-fat diet (HFD) and streptozotocin (STZ). Body weight, food intake, and glucose tolerance test (GTT) were measured at indicated time points. Apoptosis of the beta cells was measured by Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL) assay. We also assessed the macrophage content and NLRP3 expression in the rat model. Furthermore, macrophage reconstitution was performed after DJB surgery. Beta cell function and NLRP3 inflammasome pathway were re-evaluated in wild-type macrophage reconstitution group and NLRP3-knockdown macrophage reconstitution group. RESULTS DJB surgery group rats displayed rapid and sustained improvement in glucose tolerance. Decreased apoptosis and improved secretion function of the beta cells were observed in DJB surgery group. NLRP3 inflammasome pathway in infiltrating macrophages was also suppressed after DJB surgery. Moreover, diabetic remission acquired by DJB sustained in NLRP3-knockdown macrophage reconstitution group, while extinguished in group reconstituted with wild-type macrophage. CONCLUSIONS NLRP3 inflammasome deactivation in infiltrating macrophages is involved in marked beta cell function improvement after DJB surgery.

Downregulation of lncRNA MALAT1 contributes to renal functional improvement after duodenal-jejunal bypass in a diabetic rat model

Ameliorated renal function has been reported after bariatric surgery, but the mechanisms underlying this phenomenon are not well-studied. To investigate whether the long non-coding RNA (lncRNA) MALAT1 mediates the amelioration of diabetic nephropathy after duodenal-jejunal bypass (DJB) surgery, rats were assigned randomly into four groups: diabetic (DM) group, DM with DJB surgery group, DM with sham surgery group, and healthy control group. Food intake, body weight, oral glucose tolerance test (OGTT), urine albumin excretion rate (UAER), and glomerular filtration rate (GFR) were measured and histological examination of renal sections was performed. For in vitro study, HK-2 cells were cultured under various glucose concentrations following MALAT1 siRNA transfection. Expression levels of MALAT1, SAA3, IL-6, and TNF-α in rat renal tissues or HK-2 cell lines were evaluated by qRT-PCR and/or ELISA. Results showed DJB surgery improved the renal function of diabetic rats, as indicated by ameliorated UAER and GFR and attenuated glomerular hypertrophy. Expression of MALAT1 and its downstream target SAA3 was significantly downregulated in renal tissues after DJB, which in turn decreased the expression of the pro-inflammatory cytokines IL-6 and TNF-α. Knockdown of MALAT1 in HK-2 cell lines further confirmed that expression levels of SAA3, IL-6, and TNF-α were regulated by MALAT1 under both low- and high-glucose conditions. Our findings suggest that MALAT1 is implicated in the improvement of renal function after DJB through regulation of its downstream targets SAA3, IL-6, and TNF-α.