改变胃旁路术Roux肠袢长度对GK大鼠糖代谢改善的影响

目的研究胃旁路术(RYGB)中,不同Roux肠袢长度对GK大鼠糖代谢和激素分泌的影响。方法将GK大鼠随机分为5组,未处理组(GK-Blank)、假手术饮食对照组(GK-PF-Sham)和3组RYGB手术组。手术组根据Roux肠袢长度3 cm、12 cm和30cm分为GK-S-3 cm组、GK-S-12 cm组、GK-S-30 cm组,同时用Wistar大鼠作为正常对照。定期测量大鼠体质量;术后6个月,对各组大鼠行口服糖耐量试验、腹腔糖耐量试验和胰岛素耐量试验,并眼眶取血检测血中胰岛素及激素含量。结果 GK-S-12 cm组及GK-S-30 cm组大鼠体质量显著低于GK-Blank组,GK-S-3 cm组在各实验时间点均未观察到明显体质量下降。GK-S-30 cm组在胰岛素抵抗、口服和腹腔注射葡萄糖耐受性上,均显著优于GK-S-3 cm组与GK-Blank组。经葡萄糖灌胃,3个手术组胰岛素分泌、GLP-1水平都有明显改善,显著不同于GK-Blank组及GK-PF-Sham组。结论胃旁路手术中,通过构建不同的Roux肠袢长度,可不同程度缓解2型糖尿病病症。增加Roux袢长度,更有助于改善糖耐量,并提高胰岛素敏感性。     

2型糖尿病患者胃旁路术后1年糖代谢变化规律的研究

目的 探讨2型糖尿病(T2DM)患者胃旁路术(GBP)后的糖代谢变化规律. 方法 2006年1月至2007年6月期间,我院普外科住院的129例T2DM患者,按HbA_1c分为:A组,HbA_1c 7%～7.9%;B组,HbA_1c8%～9%;C组,HbA_1c>9%.三组患者均实施GBP手术,术前和术后1、3、6、12个月检查OGTT、胰岛素释放试验、C-P释放试验、HbA_1c和BMI,计算胰岛素分泌指数,术后随访1年.结果 (1)与术前相比,术后各组BMI呈下降趋势,C组术后明显降低,差异有统计学意义(P<0.01);(2)与术前相比,术后FPG水平逐渐下降至术后12个月,差异有统计学意义(P<0.01);(3)术后各组FIns水平无统计学差异;(4)与术前相比,A组术后12个月FC-P水平明显升高(P=0.006);(5)与术前相比,术后HbA_1c逐渐下降,术后12个月差异有统计学意义(P均<0.01);(6)与术前相比,A组术后12个月△I_(30)明显改善(P<0.01). 结论 GBP后T2DM患者糖代谢明显改善.     

Roux-en-Y胃旁路术对肥胖糖尿病大鼠糖脂代谢及炎症水平的影响

目的 研究Roux-en-Y胃旁路术（RYGB）对自发型肥胖糖尿病（ZDF）大鼠模型糖脂代谢及全身炎症水平的影响.方法 30只雄性ZDF大鼠采用完全随机分组方法分为3组：RYGB手术组（n=10）、匹配饮食控制对照组（PF组,n=10）、自由进食对照组（AL组,n=10）.定期测量大鼠体重与摄食量.在术前及术后10周时,对各组大鼠行口服糖耐量试验,检测血糖、血脂、肝脏转氨酶及血清肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）与单核细胞趋化蛋白1（MCP-1）等炎症相关指标,处死各组大鼠后取附睾脂肪,采用实时定量-聚合酶链反应（RT-PCR）方法检测脂肪细胞TNF-α、IL-1β与MCP-1 mRNA表达水平.组间数据比较采用t检验与方差分析.结果 术后10周口服糖耐量试验结果表明,RYGB组、PF组及AL组在各个时间点的血糖值比较均有统计学差异[分别为：基线空腹血糖（FPG）：（6.8±0.5）、（8.7±2.2）、（20.6±3.0） mmol/L,F=12.4,P＜0.05;30 min：（14.0±0.8）、（19.1±4.3）、（31.7±0.9）mmol/L,F=20.1,P＜0.05;60 min：（15.4±1.1）、（20.2±7.1）、（33.0 ±0.3）mmol/L,F =22.5,P ＜0.05;90 min：（13.2 ±0.6）、（20.0±5.8）、（32.4±0.4）mmol/L,F=14.7,P ＜0.05;120 min：（8.3 ±0.3）、（14.0±5.2）、（29.1±1.2）mmol/L,F =20.5,P ＜0.05].血清总胆固醇（TC）、游离脂肪酸（FFA）水平显著低于PF组和AL组[分别为：TC：（3.82±0.13）比（4.10 ±0.37）比（5.25±0.25） mmol/L,F=15.3,P＜0.05,FFA：（0.47±0.14）比（0.93±0.08）比（0.78 ±0.06） mmol/L,F=3.4,P＜0.05].RYGB组大鼠血清TNF-α、IL-1β水平均较AL组明显下降[分别为TNF-α（124 ±23）比（532±52）mmol/L,t =5.8,P＜0.05;IL-1β（61±l6）比（250±32）mmol/L,t=4.3,P＜0.05],且脂肪组织中上述两种炎症因子mRNA在3组大鼠中的表达趋势与血清水平基本一致;而MCP-1在3组中表达无统计学差异（均P＞0.05）.结论 Roux-en-Y胃旁路术能显著改善肥胖2型糖尿病大鼠的糖脂代谢,减轻脂肪肝及全身炎症水平,且这种改善作用不依赖于摄食量减少.     

十二指肠空肠旁路术对非肥胖2型糖尿病GK大鼠的疗效及机制初探

雄性GK和Wistar大鼠各18只,随机分为GK大鼠手术组(A组)和假手术组(B组)、Wistar大鼠手术组(C组)和假手术组(D组),每组9只。检测术前及术后第1、4、8周各组体重、空腹血糖、血浆胰高血糖素样肽-1(glucagon-likepeptide-1 GLP-1)水平,同时测术后第8周小肠组织中GLP-1水平。结果:A组术后8周空腹血糖由(7.69±0.74)pmol/L下降到(5.95±0.78)mmol/L(P<0.01),空腹GLP-1由(7.69±0.74)pmol/L上升到(29.00±3.94)pmol/L(P<0.01),空腹血糖与血浆及组织GLP-1水平均成负相关(P<0.01),组织GLP-1水平与血浆GLP-1水平成正相关(P<0.01)。B组手术前后空腹血糖与GLP-1无明显变化。结论:DJB能显著改善非肥胖2型糖尿病大鼠的血糖,且不依赖体重下降,提示临床上非肥胖的2型糖尿病患者也可能通过手术达到降糖效果。DJB的降糖作用可能与术后血浆及肠道组织中GLP-1分泌增多起作用。     

胃旁路术对2型糖尿病大鼠胰岛β细胞凋亡的影响

目的研究胃旁路术(RYGB)对2型糖尿病大鼠胰岛β细胞凋亡的影响。方法取10周龄雄性SD大鼠60只,随机分成对照组,2型糖尿病控制大鼠手术组(RYGB)和假手术组(S-RYGB)各20只。2型糖尿病控制大鼠以高脂高糖食物喂养并腹腔小剂量链脲佐菌霉素(STZ)注射以诱导大鼠成为2型糖尿病模型。注射STZ 3 d后测大鼠空腹血糖≥16.7 mmol/L为成功糖尿病模型。测量术前和术后1、2、3、4 w各实验组动物的体重和空腹血糖,术后4 w胰腺组织取材。原位末端标记法(TUNEL)检测胰岛细胞凋亡;应用免疫组化检测β-catenin和caspase-12蛋白的表达。结果术后4 w RYGB组空腹血糖下降到(3.9±0.7)mmol/L,体重下降至(238.0±16.6)g,明显低于同时间点S-RYGB组(P0.05)。术后4 w RYGB组胰岛凋亡率为(4.01±0.39)%,与S-RYGB组(17.94±0.53)%相比较,差异显著(P0.05)。术后4 w RYGB组大鼠胰岛细胞β-catenin和caspase-12蛋白阳性率表达与S-RYGB组比较差异(P0.05)。结论 RYGB能显著降低糖尿病大鼠血糖可能是通过促进胰岛β细胞内β-catenin蛋白增加,激活wnt通路,减少caspase-12蛋白表达从而抑制β细胞凋亡来实现。     

胃旁路术治疗2型糖尿病的研究进展

全球糖尿病的发病率逐年上升,现有的规范化内科治疗仍不能完全阻止其病情进展及其并发症的发生,其治疗已成为世界性的难题.减重手术治疗2型糖尿病已在临床使用多年,其中应用最广泛的是胃旁路术,它可引起持久的体重减轻、缓解肥胖相关并发症,尤其是2型糖尿病.然而其治疗机制、适用人群、术后部分患者糖尿病复发的机制尚不明确,有待进一步研究阐明.     

保留全胃、不同区段小肠转流术后GK大鼠糖代谢变化规律的研究

目的 建立保留全胃、不同区段小肠转流手术动物模型,探讨术后GK大鼠糖代谢的变化规律.方法 GK大鼠20只随机分为4组(n=5),Ⅰ组:假手术组;Ⅱ组:十二指肠转流组;Ⅲ组:空肠转流组;Ⅳ组:回肠转流组.分别于术前及术后4周行口服糖耐量试验及胰岛素耐量试验,计算胰岛素敏感指数(ISI). 结果 (1)全部GK大鼠术后均长期存活;(2)与Ⅰ组空腹血糖相比,各实验组术后空腹血糖明显下降;(3)与Ⅰ组血糖水平相比,各实验组在OGTT各时间点血糖水平明显下降;(4)与术前ISI相比,各实验组术后ISI增加,以Ⅲ组、Ⅳ组更为显著. 结论 成功建立保留全胃、不同区段小肠转流手术的GK大鼠模型;GBP效应区域是回肠;术后GK大鼠糖代谢改善与胰岛素敏感性增加有关,与胃容积无关.     

Ghrelin与能量平衡及糖代谢的关系

Ghrelin是生长激素促分泌物受体的第一个内源性配体,具有促进生长激素分泌、促进摄食、减少脂肪利用等作用,并与胰岛素、瘦素等相互作用,影响能量平衡及糖代谢,因而与肥胖、胰岛素抵抗及2型糖尿病密切相关。进一步研究ghrelin的作用对研究肥胖、胰岛素抵抗、2型糖尿病的发生、发展过程具有指导意义。     

胃旁路术减肥同时改善糖代谢的机制

胃旁路术在平稳减肥的同时能增加胰岛素敏感性,改善糖代谢紊乱。其机制包括胃减容以减少摄入,前肠旁路致胃肠-胰岛轴改变引起多种胃肠激素如ghrelin、胰升糖素样肽-1（GLP-1）、葡萄糖依赖性促胰岛素多肽、多肽YY等变化改善了胰岛素的分泌和（或）活性,脂肪细胞因子的改变如脂联素水平升高、瘦素及酰化刺激蛋白降低和一些炎性反应因子如C反应蛋白、白细胞介素-6（IL-6）的变化等。     

胃旁路术与胆胰转流术治疗2型糖尿病机制的研究

目的 比较胃旁路术(GBP)与胆胰转流术(BPD)对非胰岛素依赖性糖尿病大鼠的治疗效果,探讨其机制.方法 40只糖尿病GK大鼠按数字表法随机分为GBP组、BPD组、饮食控制组和对照组,每组10只.GBP组、BPD组分别行GBP及BPD手术;饮食控制组大鼠每天给予基础饲料15 g,自由进水;对照组不限食量.记录手术时间、死亡率.每周测空腹体重.检测治疗前及治疗后1、2、3、4、8、16周的空腹血糖、瘦素、胰岛素样生长因子-1(IGF-1)水平.结果 GBP组平均手术时间为(25±4)min,BPD组为(35±6)min;GBP组大鼠死亡1只,BPD组死亡3只,两组差异均有统计学意义(P值均＜0.01).治疗前各组大鼠血糖、瘦素及IGF-1水平无统计学差异.治疗后对照组大鼠血糖及瘦素均无明显变化.饮食控制组大鼠治疗后2周起血糖及瘦素水平开始下降,第4周时显著降低,并持续至16周(P＜0.05),但血IGF-1水平无明显变化.GBP组与BPD组大鼠治疗后2周起血糖及瘦素水平开始下降,而血IGF-1水平开始升高,并持续至16周[血糖:(6.8±1.0)、(6.3±0.8)mmol/L比(13.9±2.6)、(14.1±2.4)mmol/L;瘦素:(16.1±3.3)、(17.2±3.2)pg/ml比(29.4±3.9)、(29.4±3.9) pg/ml;IGF-1:( 166.1±8.3)、(142.2±8.2) ng/L比(119.4±8.8)、(109.8±7.9)ng/L,P值均＜0.01],但这两组的血糖及瘦素水平无统计学差异;而GBP组大鼠血IGF-1水平较BPD组升高更显著(P＜0.05).结论 GBP和BPD均能较好地控制糖尿病大鼠的血糖水平,其机制可能与瘦素的降低及IGF-1的升高有关.GBP在手术时间、死亡率及增加血IGF-1水平等方面优于BPD.     

Eugenosedin-A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide-induced diabetic rats

This study examined the effects of eugenosedin-A (Eu-A) in a streptozotocin (STZ)/nicotinamide-induced rat model of type II diabetes mellitus (T2DM). Six-week-old Sprague–Dawley rats were randomly divided into three groups: (1) RD group, normal rats fed a regular diet (RD), (2) DM group, T2DM rats fed a high-fat diet, and (3) Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day). After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK) in liver and skeletal muscle and decreased protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), IRS-2, AMP-activated protein kinase (AMPK), glucose transporter-4 (GLUT-4), glucokinase (GCK), and peroxisome proliferator-activated receptor γ (PPAR-γ). STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK) and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.     

Predictors of postpartum glucose metabolism disorders in women with gestational diabetes mellitus

Background and aimsPostpartum glucose metabolism disorders are a common problem in women with gestational diabetes mellitus (GDM). They are often underdiagnosed since many patients do not attend the postpartum screening. This study aims to assess predictors of postpartum glucose metabolism disorders and type 2 diabetes mellitus (T2DM) after GDM.Material and methodsRetrospective study in women with GMD who underwent postpartum screening for glucose metabolism disorders (n = 2688). Logistic regression was used in the statistical analysis.Results24.6% of women had postpartum glucose metabolism disorder. In multivariate analysis, pre-pregnancy body mass index (BMI) 25–30 kg/m² (OR 1.46, 95%CI 1.05 to 2.02) or BMI ≥30 kg/m² (OR 2.62, 95%CI 1.72 to 3.96), diagnosis of GDM before 20 weeks of pregnancy (OR 2.33, 95%CI 1.57 to 3.46), fasting plasma glucose after diagnosis of GDM ≥90 mg/dl (OR 2.12, 95%CI 1.50 to 2.98), postprandial glucose ≥100 mg/dl (OR 1.47, 95%CI 1.09 to 2.99), and HbA1c in the third trimester of pregnancy ≥5.3% (2.04, 95%CI, 1.52 to 2.75) were independent predictors for any postpartum glucose metabolism disorder.Conclusionpostpartum screening for T2DM should be performed in all women with GDM, and it is especially important not to lose follow-up in those with one or more predictive factors.     

Effect of berberine on hyperglycaemia and gut microbiota composition in type 2 diabetic Goto-Kakizaki rats

BACKGROUND A recent investigation showed that the prevalence of type 2 diabetes mellitus(T2DM)is 12.8%among individuals of Han ethnicity.Gut microbiota has been reported to play a central role in T2DM.Goto-Kakizaki(GK)rats show differences in gut microbiota compared to non-diabetic rats.Previous studies have indicated that berberine could be successfully used to manage T2DM.We sought to understand its hypoglycaemic effect and role in the regulation of the gut microbiota.AIM To determine whether berberine can regulate glucose metabolism in GK rats via the gut microbiota.METHODS GK rats were acclimatized for 1 wk.The GK rats were randomly divided into three groups and administered saline(Mo),metformin(Me),or berberine(Be).The observation time was 8 wk,and weight,fasting blood glucose(FBG),insulin,and glucagon-like peptide-1(GLP-1)were measured.Pancreatic tissue was observed for pathological changes.Additionally,we sequenced the 16S rRNA V3-V4 region of the gut microbiota and analysed the structure.RESULTS Compared with the Mo group,the Me and Be groups displayed significant differences in FBG(P<0.01)and GLP-1(P<0.05).A significant decrease in weight and homeostatic model assessment-insulin resistance was noted in the Be group compared with those in the Me group(P<0.01).The pancreatic islets of the Me-and Be-treated rats showed improvement in number,shape,and necrosis compared with those of Mo-treated rats.A total of 580 operational taxonomic units were obtained in the three groups.Compared to the Mo group,the Me and Be groups showed a shift in the structure of the gut microbiota.Correlation analysis indicated that FBG was strongly positively correlated with Clostridia_UCG-014(P<0.01)and negatively correlated with Allobaculum(P<0.01).Body weight showed a positive correlation with Desulfovibrionaceae(P<0.01)and a negative correlation with Akkermansia(P<0.01).Importantly,our results demonstrated that Me and Be could significantly decrease Bacteroidetes(P<0.01)and the Bacteroidetes/Firmicutes ratio(P<0.01).Furthermore,Muribaculaceae(P<0.01;P<0.05)was significantly decreased in the Me and Be groups,and Allobaculum(P<0.01)was significantly increased.CONCLUSION Berberine has a substantial effect in improving metabolic parameters and modulating the gut microbiota composition in T2DM rats.     

腹腔镜下胃旁路手术治疗2型糖尿病26例

目的:总结腹腔镜胃旁路手术治疗2型糖尿病的初步经验.方法:回顾性分析苏州大学附属第一医院2010-05/2010-11开展的腹腔镜下胃旁路手术(LRYGB)治疗2型糖尿病26例的临床资料.患者纳入标准:BMI≥24 kg/m2、糖化血红蛋白(HbAlc)≥7％、空腹血清C肽≥1μg/L,患者对手术有强烈的要求,依从性好...     

Lack of effects of angiotensin-converting enzyme (ACE)-inhibitors on glucose metabolism in type 1 diabetes

To evaluate the impact of ACE-inhibitors on insulin-mediated glucose uptake, glucose-induced glucose uptake, and hepatic glucose production, a sequential glucose clamp was performed in eight normotensive Type 1 diabetic patients after 3 weeks of enalapril therapy 20 mg day-1 and during control conditions. The experiments were carried out in random order. Mean arterial blood pressure was significantly reduced during ACE-inhibition (95 +/- 3 (+/- SE) vs 84 +/- 3 mmHg; p less than 0.02), while blood glucose control as assessed by HbA1c was unaltered (7.9 +/- 0.5 vs 7.6 +/- 0.5%). The night prior to the study normoglycaemia was maintained by a Biostator. A two-step hyperinsulinaemic euglycaemic clamp (insulin infusion rate 0.3 and 0.8 mU kg-1 min-1) was followed by a hyperinsulinaemic and hyperglycaemic clamp (insulin infusion rate 0.8 mU kg-1 min-1, plasma glucose 11 mmol l-1). Insulin concentrations were comparable with and without enalapril treatment. During the hyperinsulinaemic clamps isotopically determined glucose disposal was unchanged (low dose 2.5 +/- 0.3, high dose 4.3 +/- 0.7 vs 2.6 +/- 0.3 and 4.3 +/- 0.7 mg kg-1 min-1, enalapril vs control). Glucose-induced glucose disposal (9.2 +/- 1.2 vs 9.1 +/- 1.2 mg kg-1 min-1) was also similar, as were non-protein respiratory exchange ratios (indirect calorimetry). Glucose production was not changed by enalapril. In conclusion, treatment with enalapril has no significant effect on glucose metabolism in Type 1 diabetes.