马里苷、黄诺玛苷对db/db小鼠肠道菌群的影响及相关性

目的探索两色金鸡菊中黄酮类成分马里苷、黄诺玛苷对db/db小鼠肠道菌群的影响。方法将db/m小鼠作为正常对照组,db/db小鼠分为db/db模型组、db/db+恩格列净(db/db+Empagliflozin)组、db/db+马里苷(db/db+Marein)组、db/db+黄诺玛苷(db/db+Flavanomarein)组,每组8只。采用实时荧光定量PCR(RT-qPCR)的方法检测小鼠粪样中Bacteroides ovatus、Ruminococcus gnavus的变化,并运用Pearson检验分析Bacteroides ovatus、Ruminococcus gnavus的变化与2型糖尿病相关表型的相关性。结果 (1)干预12周后与db/m组相比,db/db组小鼠粪样中Bacteroides ovatus水平显著降低(P0.010);恩格列净(P0.001)、马里苷(P0.050)、黄诺玛苷(P0.001)干预后能显著升高其含量,差异具有统计学意义。(2)与db/m组相比,db/db组小鼠粪样中Ruminococcus gnavus水平显著升高(P0.050);恩格列净(P0.050)、马里苷(P0.050)干预后能显著降低其含量,差异具有统计学意义。(3)Bacteroides ovatus水平与空腹血糖(FBG)、三酰甘油(TG)呈负相关(r=-0.420,P=0.021;r=-0.474,P=0.008);Ruminococcus gnavus水平与FBG、TG呈正相关(r=0.397,P=0.030;r=0.404,P=0.027)。结论马里苷、黄诺玛苷可以调节小鼠肠道菌群的变化,这可能是其抗糖尿病的重要机制。     

乳源性复合益生菌促进db/db糖尿病小鼠白色脂肪棕色化的研究

目的研究乳源性复合益生菌对db/db糖尿病小鼠白色脂肪棕色化细胞因子解偶联蛋白1(UCP1)、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC1α)、R结构域蛋白16(PRDM16)表达的影响。方法将6周龄的SPF级db/db糖尿病雄性小鼠适应性喂养1周,随机分为糖尿病模型组、罗格列酮组及复合益生菌高剂量组和低剂量组,SC57BL/Ks雄性小鼠为正常对照组,每组8只。血糖仪检测不同时段空腹血糖(FBG)水平,ELISA法检测糖化血红蛋(HbA1c)含量,取各组小鼠皮下白色脂肪组织,HE染色观察脂肪组织形态,用Real time-PCR检测各组白色脂肪组织中UCP1、PGC1α、PRDM16 mRNA表达水平以及Western Blot检测各组脂肪组织中UCP1的表达。结果与模型组相比,复合益生菌组FBG、HbA1c水平明显下降,并且复合益生菌能够明显增加脂肪组织多室脂肪细胞数量,具有棕色化的趋向,并能够显著提高UCP1、PGC1α、PRDM16的mRNA表达和UCP1表达量。结论本研究发现乳源性复合益生菌能够促进白色脂肪棕色化从而改善胰岛素抵抗。     

大黄素降糖及改善脂质代谢的实验研究

目的:探讨大黄素对2型糖尿病模型db/db小鼠血糖及血脂水平的影响.方法:4周龄16只db/db雄性小鼠随机分为治疗组和对照组,每组8只;治疗组经灌胃每天给予100mg/kg大黄素;对照组灌胃给予相仿体积的生理盐水,开始10天每天算进食量,每周测空腹血糖及体重1次,连续干预8周,干预前及实验结束前1周测胰岛素耐量,干预结束后于颈动脉取血测血脂水平(HDLC、LDL-C、TG、TC).结果:①大黄素干预不影响db/db小鼠的进食量,与对照组比较,P＞0.05;②大黄素可显著减轻db/db小鼠体重,与对照组比较,P＜0.05;③大黄素可改善db/db小鼠胰岛素敏感性,降低小鼠的空腹血糖水平,与对照组比较,P＜0.05或P＜0.01;④大黄素可降低db/db小鼠血TG、TC、LDL-C水平,P＜0.01.结论:大黄素可有效地改善db/db小鼠的糖脂紊乱状态,其降糖及改善血脂代谢机制值得进一步深入研究.     

大黄素降糖及改善脂质代谢的实验研究

目的：探讨大黄素对2型糖尿病模型db/db小鼠血糖及血脂水平的影响。方法：4周龄16只db/db雄性小鼠随机分为治疗组和对照组,每组8只;治疗组经灌胃每天给予100mg/kg大黄素;对照组灌胃给予相仿体积的生理盐水,开始10天每天算进食量,每周测空腹血糖及体重1次,连续干预8周,干预前及实验结束前1周测胰岛素耐量,干预结束后于颈动脉取血测血脂水平（HDL-C、LDL-C、TG、TC）。结果：①大黄素干预不影响db/db小鼠的进食量,与对照组比较,P〉0.05;②大黄素可显著减轻db/db小鼠体重,与对照组比较,P〈0.05;③大黄素可改善db/db小鼠胰岛素敏感性,降低小鼠的空腹血糖水平,与对照组比较,P〈0.05或P〈0.01;④大黄素可降低db/db小鼠血TG、TC、LDL-C水平,P〈0.01。结论：大黄素可有效地改善db/db小鼠的糖脂紊乱状态,其降糖及改善血脂代谢机制值得进一步深入研究。     

急性高血糖影响小鼠第一时相胰岛素分泌的机制

目的观察急性高血糖影响小鼠第一时相胰岛素分泌的功能及形态学变化特点。方法给C57/BL 6J小鼠完成颈静脉插管后输注20%高糖溶液4 h,建立急性糖毒性小鼠模型,行腹腔葡萄糖耐量实验(intraperitoneal glucose tolerance test,IPGTT)及口服葡萄糖耐量实验(oral glucose tolerance test,OGTT)评价葡萄糖耐量及胰岛素分泌功能。HE染色及电镜观察胰岛形态变化及细胞内胰岛素分泌颗粒亚细胞结构变化。结果 IPGTT实验中急性糖毒性组15 min血糖值较对照组显著增加[(10.3±0.33)mmol/L vs(19.3±1.66)mmol/L],上升87%(P0.05),OGTT实验中30 min血糖值较对照组显著增加[(9.8±0.31)mmol/L vs(18.16±1.01)mmol/L],升高85%(P0.05),且早期胰岛素分泌高峰受损且分泌延迟。GSIS实验中急性糖毒性组在基础状态时(葡萄糖浓度2.8 mmol/L)和高糖(16.7 mmol/L)刺激后,胰岛素分泌较对照组显著降低[(0.481±0.003)ng/m L vs(0.702±0.121)ng/m L,(2.43±0.03)ng/m L vs(4.07±0.34)ng/m L],分别下降46%和67%(P0.05);胰岛素含量测定结果显示,急性糖毒性组比对照组降低[(97.01±2.05)ng/m L vs(65.12±0.42)ng/m L,(121.40±0.58)ng/m L vs(62.7±0.48)ng/m L],下降49%和94%(P0.05)。HE染色显示急性糖毒性胰岛边界不规则、内部细胞排列不整;透射电镜可见细胞内胰岛素分泌颗粒空泡,线粒体嵴断裂。结论急性葡萄糖毒性使胰岛β细胞内胰岛素储备减少,导致第一时相分泌胰岛素峰值降低及延迟。     

菠萝蜜低聚肽对db/db小鼠炎症反应、血糖及血脂的影响

目的：研究菠萝蜜低聚肽（JOPs）干预对db/db糖尿病模型小鼠炎症反应、血糖及血脂的影响作用。方法：选择db/db糖尿病小鼠模型,将其随机分为3个JOPs组（0.2、0.4、0.8g/kg·BW）以及糖尿病模型对照组、二甲双胍对照组、乳清蛋白对照组,并选用db/m小鼠作为非糖尿病小鼠空白对照。经过为期6个月的干预,检测小鼠空腹血糖（FPG）、血清胰岛素（INS）、白细胞介素6（IL 6）、白细胞介素8（IL 8）、白细胞介素10（IL 10）和肿瘤坏死因子α（TNF α）、C反应蛋白（CRP）以及脂代谢指标。结果：JOPs可显著降低db/db糖尿病小鼠空腹血糖水平及胰岛素抵抗指数;可使血清IL 6、TNF α、总胆固醇（TC）和甘油三酯（TG）显著降低,并使高密度脂蛋白胆固醇（HDL C）显著升高。结论：JOPs干预可有效降低糖尿病小鼠的血糖水平,改善胰岛素抵抗,同时有效调节炎症反应及血脂代谢。     

姜黄素对db/db小鼠基因组DNA甲基化的影响

目的:观察姜黄素对2型糖尿病模型db/db小鼠糖尿病症状的改善作用,并从表观遗传角度分析其对小鼠外周血DNA甲基化水平的影响。方法:2型糖尿病模型db/db小鼠随机分为糖尿病组和姜黄素干预组(给予250 mg/kg姜黄素溶液),连续灌胃8周。OGTT检测葡萄糖耐量,ELISA法测定空腹胰岛素并计算HOMA-IR和HOMA-β,RRBS技术检测外周血基因组DNA甲基化水平。结果:与糖尿病组相比,姜黄素干预小鼠的血糖、空腹胰岛素和HOMA-IR显著降低,葡萄糖耐量显著改善(P<0.05);且小鼠外周血基因组启动子区、CGI岸和5’-非编码区CpG甲基化水平显著降低(P<0.05);对两组间差异甲基化基因进行功能富集分析,筛选出前10位显著富集的可能与2型糖尿病相关的差异基因包括Hdac7、Micall1、Vangl2、Dhcr24、Kcnj8、Gnas、Tcf7l2、Dgkh、Dlgap1和Plekhg4。结论:姜黄素能够改善db/db小鼠的葡萄糖耐量及胰岛素抵抗,并且其外周血中存在显著低甲基化改变,提示姜黄素可能是通过抑制糖尿病小鼠中某些基因的异常甲基化修饰而发挥抗糖尿病作用。     

松果菊苷对db/db糖尿病小鼠心肌的保护作用

糖尿病心肌病（diabetic cardiomyopathy, DCM）是指发生于糖尿病患者,不能用冠心病、高血压性心脏病及其他心脏病变来解释的心肌疾病。目前,DCM的病因和发病机制尚未完全阐明,且缺乏特异性治疗手段。中药管花肉苁蓉提取物松果菊苷（echinacoside, ECH）对心肌细胞具有保护作用。以db/m小鼠为正常对照组（db/m组）,db/db小鼠分为模型组（db/db组）和ECH干预组（db/db+ECH组）,探讨了ECH对糖尿病db/db小鼠心肌的影响及机制。db/db+ECH组小鼠给予松果菊苷灌胃,db/m组和db/db组小鼠给予0.9%氯化钠溶液灌胃。心脏超声观察心脏功能,Masson染色观察组织胶原纤维含量,逆转录聚合酶链式反应检测Ⅰ型胶原和Ⅲ型胶原mRNA的表达,蛋白质免疫印迹技术检测转化生长因子-β1（transforming growth factor-β1, TGF-β1）、phospho-Smad2（p-Smad2）和phospho-Smad3（p-Smad3）的表达。结果显示,ECH能够改善db/db小鼠左心室肥大和心脏功能,降低胶原沉积（P<0.05）。ECH能够降低Ⅰ型和Ⅲ型胶原mRNA的表达（P<0.01）,下调TGF-β1、p-Smad2和p-Smad3蛋白的表达（P<0.05）。ECH对糖尿病心肌的保护作用可能与负反馈调节TGF-β1/Smads信号通路相关,研究结果为DCM的早期干预提供了新思路。     

跑台运动通过依赖p38MAPK信号通路上调FNDC5改善db/db小鼠非酒精性脂肪性肝病

该文旨在探讨8周跑台运动改善Ⅱ型糖尿病小鼠非酒精性脂肪性肝病(nonalcoholic fatty liver disease, NAFLD)的作用及分子机制。将SPF级别的8周龄的雄性m/m小鼠作为阴性对照组(Con组), 8周龄的雄性db/db小鼠随机分为4组:Ⅱ型糖尿病模型组(db组)、Ⅱ型糖尿病跑台运动组(db+EX组)、Ⅱ型糖尿病跑台运动联合p38MAPK抑制剂组(db+EX+SB203580组)、单纯p38MAPK抑制剂组(db+SB203580组),每组各10只。腹腔注射p38MAPK抑制剂2 h后进行跑台运动干预,每天运动干预40 min,每周5天,连续8周。通过小鼠体质量、血糖、肝体比、血脂以及HE、油红和Masson染色评价运动干预对NAFLD的干预效果。通过Western blot和qRT-PCR测定相关蛋白和mRNA表达水平。结果显示, 8周跑台运动可以明显减轻db/db小鼠体质量、血糖、肝体比值的增加,降低小鼠血脂水平。运动干预减少了小鼠肝脏脂肪变性、胶原蛋白沉积及ACC1、SREBF1脂肪从头合成酶的表达水平。单纯p38MAPK抑制剂干预加重了肝脏脂肪变性和...     

核桃低聚肽对db/db小鼠血糖的影响作用研究

目的：研究核桃低聚肽（walnut oligopeptides,WOPs）干预对db/db糖尿病模型小鼠血糖的影响作用。方法：选择db/db糖尿病小鼠模型,将其随机分为3个核桃低聚肽组（220、440、880mg/kg·BW）、糖尿病模型对照组、二甲双胍对照组、乳清蛋白对照组;并选用db/m小鼠作为非糖尿病小鼠空白对照。经过为期6周的干预,检测小鼠空腹血糖、餐后血糖以及糖耐量实验血糖曲线下面积。结果：核桃低聚肽（880mg/kg·BW）可降低db/db糖尿病小鼠空腹血糖水平和餐后血糖水平,同时能有效改善糖耐量（P＜0.05）。结论：核桃低聚肽干预可有效降低糖尿病小鼠的血糖水平,改善糖耐量,具有辅助降血糖功能。     

桂皮醛对高脂喂养小鼠糖脂代谢影响的实验研究

目的：探讨口服桂皮醛对高脂喂养小鼠（C57BL/6J 背景）糖脂代谢的影响。方法：采用雄性C57BL/6J小鼠作为研究对象,分 正常对照组（6 只）,高脂组（6 只）,高脂+ 桂皮醛（40 mg/kg,每天1 次）干预组（6 只）。桂皮醛以0.5 %羧甲基纤维素钠（CMC-Na） 溶解后口服灌胃,每天1 次;正常对照组和高脂组给予灌服等体积的CMC-Na,每天1 次,干预时间为3 月。每周观察体重、空腹血 糖,实验结束后观察胰岛素耐量（IPITT）、葡萄糖耐量（IPGTT）,观察各组小鼠的血脂水平（TC,TG,LDL-C,HDL-C）、胰岛素水 平、肠系膜脂肪重量及以HE 染色观察脂肪细胞形态。结果：在脂代谢方面,桂皮醛干预可显著防止高脂喂养小鼠的体重和血脂水 平的升高;高脂喂养小鼠肠系膜脂肪重量显著增加,HE 染色提示脂肪细胞显著增大;桂皮醛可显著防止肠系膜脂肪重量的增加 及脂肪细胞的变大。而在葡萄糖代谢方面,桂皮醛可显著降低高脂喂养小鼠血糖和胰岛素水平,改善小鼠的葡萄糖耐量和胰岛素 敏感性。结论：口服桂皮醛可显著改善高脂喂养小鼠的糖、脂代谢。     

Supplementation of a novel microbial biopolymer, PGB1, from new Enterobacter sp. BL-2 delays the deterioration of type 2 diabetic mice

Antidiabetic effects of a novel microbial biopolymer (PGB)1 excreted from new Enterobacter sp. BL-2 were tested in the db/db mice. The animals were divided into normal control, rosiglitazone (0.005%, wt/wt), low PGB1 (0.1%, wt/wt), and high PGB1 (0.25%, wt/wt) groups. After 5 weeks, the blood glucose levels of high PGB1 and rosiglitazone supplemented groups were significantly lower than those of the control group. In hepatic glucose metabolic enzyme activities, the glucokinase activities of PGB1 supplemented groups were significantly higher than the control group, whereas the PEPCK activities were significantly lower. The plasma insulin and hepatic glycogen levels of the low and high PGB1 supplemented groups were significantly higher compared with the control group. Specifically, the insulin and glycogen increases were dose-responsive to PGB1 supplement. PGB1 supplement did not affect the IPGTT and IPITT compared with the control group; however, rosiglitazone significantly improved IPITT. High PGB1 and rosiglitazone supplementation preserved the appearance of islets and insulin-positive cells in immunohistochemical photographs of the pancreas compared with the control group. These results demonstrated that high PGB1 (0.25% in the diet) supplementation seemingly contributes to preventing the onset and progression of type 2 diabetes by stimulating insulin secretion and enhancing the hepatic glucose metabolic enzyme activities.     

Antidiabetic effect of enterolactone in cultured muscle cells and in type 2 diabetic model db/db mice

Enterolactone (ENL) is formed by the conversion of dietary precursors like strawberry lignans via the gut microbiota. Urinary concentrations of lignan metabolites are reported to be significantly associated with a lower risk of Type 2 diabetes (T2D). In the present study, antidiabetic effect of ENL and its modes of action were studied in vitro and in vivo employing a rat skeletal muscle-derived cell line, L6 myocytes in culture, and T2D model db/db mice. ENL dose-dependently increased glucose uptake in L6 myotubes under insulin absent condition. This increase by ENL was canceled by compound C, an inhibitor of 5′-adenosine monophosphate-activated protein kinase (APMK). Activation (=phosphorylation) of AMPK and translocation of glucose transporter 4 (GLUT4) to plasma membrane in L6 myotubes were demonstrated by Western blotting analyses. Promotion by ENL of GLUT4 translocation to plasma membrane was also visually demonstrated by immunocytochemistry in L6 myoblasts that were transfected with glut4 cDNA-coding vector. T2D model db/db mice were fed the basal 20 % casein diet (20C) or 20C supplemented with ENL (0.001 or 0.01 %) for 6 weeks. Fasting blood glucose (FBG) levels were measured every week and intraperitoneal glucose tolerance test (IPGTT) was conducted. ENL at a higher dose (0.01 % in 20C) suppressed the increases in FBG levels. ENL was also demonstrated to improve the index of insulin resistance (HOMA-IR) and glucose intolerance by IPGTT in db/db mice. From these results, ENL is suggested to be an antidiabetic chemical entity converted from dietary lignans by gut microbiota.     

Chlorogenic Acid Improves Late Diabetes through Adiponectin Receptor Signaling Pathways in db/db Mice

The aim of this study was to examine the effects of chlorogenic acid (CGA) on glucose and lipid metabolism in late diabetic db/db mice, as well as on adiponectin receptors and their signaling molecules, to provide evidence for CGA in the prevention of type 2 diabetes. We randomly divided 16 female db/db mice into db/db-CGA and db/db-control (CON) groups equally; db/m mice were used as control mice. The mice in both the db/db-CGA and db/m-CGA groups were administered 80 mg/kg/d CGA by lavage for 12 weeks, whereas the mice in both CON groups were given equal volumes of phosphate-buffered saline (PBS) by lavage. At the end of the intervention, we assessed body fat and the parameters of glucose and lipid metabolism in the plasma, liver and skeletal muscle tissues as well as the levels of aldose reductase (AR) and transforming growth factor-β1 (TGF-β1) in the kidneys and measured adiponectin receptors and the protein expression of their signaling molecules in liver and muscle tissues. After 12 weeks of intervention, compared with the db/db-CON group, the percentage of body fat, fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) in the db/db-CGA group were all significantly decreased; TGF-β1 protein expression and AR activity in the kidney were both decreased; and the adiponectin level in visceral adipose was increased. The protein expression of adiponectin receptors (ADPNRs), the phosphorylation of AMP-activated protein kinase (AMPK) in the liver and muscle, and the mRNA and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) in the liver were all significantly greater. CGA could lower the levels of fasting plasma glucose and HbA1c during late diabetes and improve kidney fibrosis to some extent through the modulation of adiponectin receptor signaling pathways in db/db mice.     

高脂饮食诱导的C57BL／6J肥胖小鼠脂肪组织RIP140基因表达水平的研究

目的：探讨高脂饮食致肥胖小鼠脂肪组织RIP140mRNA表达水平的变化及其与胰岛素抵抗的关系。方法：将C57BL／6J雄性小鼠随机分为正常饮食（NFD）组、高脂饮食（HFD）纽分别喂养14周后,测量两组小鼠体重,以NFD组小鼠体重作为对照,选取HFD组中体重大于对照组小鼠平均体重20％的小鼠作为肥胖组小鼠。对照组和肥胖组小鼠取血测甘油三酯（TG）、总胆固醇（TC）、空腹血糖（FBG）、空腹胰岛素水平（FIns）,计算稳态模型胰岛素抵抗指数（HOMA-IR）;采用RT—PCR技术检测两组小鼠附睾脂肪组织RIP140 mRNA的表达水平,并进行统计学分析。结果：HDF组小鼠中有12只符合标准计入肥胖组。肥胖组小鼠TG、TC、FBG、Fins（P〈0．05）,HOMA-1R（P〈0．01）均明显高于对照组;肥胖组小鼠脂肪组织RIP140mRNA的表达高于对照组,差异具有统计学意义（P〈0．05）;相关分析显示小鼠脂肪组织R1P140 mRNA表达水平与TG水平呈正相关（r=0．536,P〈0．05）,与胰岛素抵抗指数呈正相关（r=0．465,P〈0．05）,而与TC、FBG、Fins水平相关分析无统计学意义（P〉0．05）。结论：高脂饮食诱导的肥胖小鼠脂肪组织RIP140 mRNA表达增加,并与胰岛素抵抗程度呈正相关。     

EPO对高脂喂养小鼠棕色脂肪组织PRDM16、FGF21表达及STAT3磷酸化水平的影响

目的：探索促红细胞生成素（EPO）对高脂饲料（HFD）喂养小鼠血糖和血浆胰岛素水平、胰岛素抵抗指数（HOMA-IR）、糖耐量,以及棕色脂肪组织中含PR结构域蛋白16（PRDM16）、信号转导与转录激活因子3（STAT3）磷酸化水平（p-STAT3/STAT3）、成纤维细胞生长因子21（FGF21）mRNA以及蛋白质表达的影响,为肥胖及其并发症的发生机制提供线索。方法：20只高脂饲料喂养的C57BL/6J雄性小鼠随机分为对照组（HFD-Con）和EPO组（HFD-EPO）,两组分别腹腔注射生理盐水和EPO（200 IU/kg）,每周3次,连续4周。4周后检测两组动物的体重、血糖与血浆胰岛素水平、HOMA-IR及糖耐量的变化;分别使用实时定量PCR法和Western blot法检测棕色脂肪组织中PRDM16、STAT3、FGF21 mRNA和蛋白质水平。结果：腹腔注射EPO 4周后,HFD-EPO组小鼠体重为（26.65±0.85）g,HFD-Con组体重为（31.50±1.60）g,P<0.01。HFD-Con组血糖为（91.06±9.86）mg/dl,HFD-EPO组为（62.79±8.09）mg/dl,P<0.01;HFD-EPO组小鼠血浆胰岛素水平为（10.56±1.06）μU/ml,HFD-Con组为（13.2±1.1）μU/ml,P<0.01。与HFD-Con组比较,HFD-EPO组的糖耐量水平显著改善,胰岛素抵抗指数下降;HFD-EPO组动物棕色脂肪组织中PRDM16、FGF21mRNA以及蛋白质表达,p-STAT/STAT3水平均显著增加,两组小鼠肝脏中FGF21 mRNA含量、血浆中FGF21含量无明显差异。结论：EPO可能通过增加棕色脂肪组织中PRDM16表达促进棕色脂肪组织的分化,降低高脂喂养小鼠的血糖水平、改善高脂喂养小鼠的糖代谢状态。     

非酒精性脂肪肝病大鼠肝脏SOCS-3的表达与吡格列酮干预研究

目的：探讨SOCS-3在非酒精性脂肪肝病（NAFLD）发病中的作用以及吡格列酮的干预作用。方法：29只雄性SD大鼠随机分为正常对照组（8只）,高脂饮食组（21只）。饲养8周后,从高质饮食组随机抽取5只大鼠证实造模成功后,将该组余下的16只大鼠继续以高脂饲料喂养,并随机分为NAFLD对照组（8只）;吡格酮干预组（8只）,予以吡格列酮3mg·kg^-1·d^-1灌胃。16周末,处死所有大鼠,检测血糖、血胰岛素、血脂、肝脏SOCS-3mRNA和SREBP-lcmRNA表达及肝脏病理学。结果：与正常对照组相比,NAFLD组血糖、血胰岛素、血脂、肝脏脂肪变水平及肝组织SOCS-3mRNA、SREBPlCmRNA表达显著上调。吡格列酮干预组sOCS．3mRNA、SREBP-1cmRNA表达较NAFLD组下调,且血糖、血胰岛素、血脂、肝脏脂肪变水平下降。SOCS-3mRNA表达水平与胰岛素抵抗指数、SREBP．1cmRNA表达水平、肝脂肪变成显著正相关。结论：SOCS-3可能通过胰岛素抵抗及上调肝组织SREBP-lcmRNA表达参与NAFLD发病,吡格列酮能抑制肝脏SOCS-3的表达,对NAFLD有一定治疗作用。     

Concordant mRNA expression of UCP-3, but not UCP-2, with mitochondrial thioesterase-1 in brown adipose tissue and skeletal muscle in db/db diabetic mice

A recent hypothesis concerning the function of uncoupling protein-3 (UCP-3) depends upon a positive relationship with mitochondrial thioesterase (MTE-1) in situations where fatty acid beta-oxidation is increased. MTE-1 mRNA levels are raised in transgenic mice overexpressing UCP-3 in skeletal muscle and we sought to extend these findings by quantifying in vivo expression of endogenous MTE-1, UCP-1, UCP-2, and UCP-3 mRNA levels in white adipose tissue, interscapular brown adipose tissue, and skeletal muscle in db/db mice. In this study we show that changes in MTE-1 mRNA levels as a result of differences between db/db vs db/+ mice or following long-term treatment of db/db mice with rosiglitazone or Wy-14,643 were more closely correlated with changes in UCP-3 than either UCP-1 or UCP-2 mRNA levels in the tissues examined. The present data contribute to the argument that UCP-3 and MTE-1 are linked within the same metabolic pathway either in response to, or as regulators of, fatty acid beta-oxidation.     

Supplementation with 9-cis β-carotene-rich alga Dunaliella improves hyperglycemia and adipose tissue inflammation in diabetic mice

Several species of the alga Dunaliella contain high levels of β-carotene. Low dietary β-carotene intake is associated with type 2 diabetes. Dunaliella contains high levels of all-trans and 9-cis isomers of β-carotene and is the best known naturally occurring nutritional source of 9-cis β-carotene. Since vitamin A has been suggested to play a role in glucose and lipid metabolism, we aimed to study the effect of Dunaliella supplementation on diabetes in mice. Ten diabetic db/db mice were fed chow diet fortified with 8 % 9-cis-rich Dunaliella powder. Ten db/db and heterozygous db/+ mice each served as controls and were fed chow diet alone. The control db/db mice developed severe hyperglycemia with fasting glucose levels reaching 400 mg dL^?1. Dunaliella significantly inhibited the elevation of plasma glucose (p?=?0.007). The area under the curve of the glucose tolerance test was 24 % lower in Dunaliella-treated mice than in the control db/db mice. Triglyceride elevation was significantly lower in the Dunaliella group than in the db/db group (p?=?0.007). The mRNA levels of several pro-inflammatory genes in adipose tissue, including monocyte chemotactic protein-1, intercellular adhesion molecule, vascular adhesion molecule-1, receptor-associated protein factor 6, and p-selectin, were elevated in the db/db group as compared to the db/+, whereas their levels were significantly lower in the Dunaliella-treated group. These results suggest that 9-cis β-carotene-rich Dunaliella may inhibit diabetes in db/db mice by reducing inflammation in adipose tissue. This study also emphasizes the importance of β-carotene isomers in our diet.     

Oxamate Improves Glycemic Control and Insulin Sensitivity via Inhibition of Tissue Lactate Production in db/db Mice

Oxamate (OXA) is a pyruvate analogue that directly inhibits the lactate dehydrogenase (LDH)-catalyzed conversion process of pyruvate into lactate. Earlier and recent studies have shown elevated blood lactate levels among insulin-resistant and type 2 diabetes subjects and that blood lactate levels independently predicted the development of incident diabetes. To explore the potential of OXA in the treatment of diabetes, db/db mice were treated with OXA in vivo. Treatment of OXA (350–750 mg/kg of body weight) for 12 weeks was shown to decrease body weight gain and blood glucose and HbA1c levels and improve insulin secretion, the morphology of pancreatic islets, and insulin sensitivity in db/db mice. Meanwhile, OXA reduced the lactate production of adipose tissue and skeletal muscle and serum lactate levels and decreased serum levels of TG, FFA, CRP, IL-6, and TNF-α in db/db mice. The PCR array showed that OXA downregulated the expression of Tnf, Il6, leptin, Cxcr3, Map2k1, and Ikbkb, and upregulated the expression of Irs2, Nfkbia, and Pde3b in the skeletal muscle of db/db mice. Interestingly, LDH-A expression increased in the islet cells of db/db mice, and both treatment of OXA and pioglitazone decreased LDH-A expression, which might be related to the improvement of insulin secretion. Taken together, increased lactate production of adipose tissue and skeletal muscle may be at least partially responsible for insulin resistance and diabetes in db/db mice. OXA improved glycemic control and insulin sensitivity in db/db mice primarily via inhibition of tissue lactate production. Oxamic acid derivatives may be a potential drug for the treatment of type 2 diabetes.