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。     

葡萄籽原花青素提取物对糖尿病小鼠血糖的影响

为了研究葡萄籽原花青素提取物(Grape Seed Proanthocyanidin Extracts,GSPE)对糖尿病小鼠的降血糖作用及其机制,本文中采用腹腔注射四氧嘧啶(ALX)构建糖尿病动物模型.造模成功后,将糖尿病小鼠分为模型对照组、格列本脲处理组、葡萄籽原花青素提取物低、中、高三个剂量(50、100、150 mg/kg)处理组,另设正常对照组.连续灌胃给药21天,每天一次,以糖尿病小鼠的体重、血清丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性胰岛素水平、空腹血糖值和糖耐量为测定指标,研究不同剂量葡萄籽原花青素提取物对糖尿病小鼠的降血糖作用及机制.结果显示原花青素高剂量组能促进体重增长,显著降低糖尿病小鼠的血糖水平和糖耐量(P＜0.01);同时降低糖尿病小鼠血清MDA水平,提高其SOD活性.通过本实验研究可以看出葡萄籽原花青素提取物具有较强的降血糖作用,降糖机制可能与其提高胰岛素水平和抗氧化能力有关.     

褐蘑菇碱提物降血糖作用研究

目的：研究褐蘑菇碱提物的降血糖作用。方法：四氧嘧啶灌胃造高血糖小鼠模型,随机分成6组,分别是正常对照组、模型对照组、高剂量组、中剂量组、低剂量组、阳性对照组,前两组以生理盐水连续灌胃7d,阳性对照组灌胃消渴丸溶液连续7d。高、中、低剂量组（100、200、400mg/kg）以褐蘑菇碱提物溶液连续灌胃7d,摘眼球取血,测定空腹血糖值。结果：高、中、低剂量组对糖尿病小鼠的降糖率分别是16.9%、20.2%和15.1%,阳性对照组的降糖率是25.1%。结论：褐蘑菇碱提物中剂量组降糖效果要优于高、低剂量组。褐蘑菇碱提物能显著降低四氧嘧啶所制备的糖尿病小鼠血糖浓度。     

虾青素对db/db小鼠糖尿病肾病的保护作用

目的：采用2型糖尿病模型db/db小鼠,观察虾青素对糖尿病肾病的保护作用。方法：db/db小鼠糖尿病肾病模型成模后随机分为：模型对照组、氯沙坦组、虾青素低剂量组、虾青素高剂量组进行干预。同窝db/m小鼠作为正常对照。其中,氯沙坦组、虾青素低剂量组、虾青素高剂量组分别采用氯沙坦10 mg/（kg·d）BW、虾青素30 mg/（kg·d）BW、虾青素60 mg/（kg·d）BW进行灌胃,氯沙坦与虾青素均用橄榄油溶解,正常对照组与模型对照组灌胃等量橄榄油。干预8w后,检测其空腹血糖、OGTT、24 h尿白蛋白、尿ACR、肌酐、尿素氮等指标。结果：低剂量虾青素对糖耐量无不良影响,并能显著降低血清尿素氮、尿蛋白、尿ACR水平。结论：低剂量虾青素具有肾脏保护作用,但不具有剂量依赖性。     

新型基因重组PACAP衍生物MPL-2的制备及其抗2型糖尿病作用研究

利用基因工程技术高效制备具有治疗2型糖尿病功能的垂体腺苷酸环化酶激活肽(PACAP)衍生物MPL-2,并以2型糖尿病小鼠(db/db小鼠)为模型在体内研究其抗2型糖尿病的生物学作用。实验结果表明:利用基因工程技术制备的PACAP27衍生多肽MPL-2的分子质量为3 902Da.,纯度达97%,其产率可达29.3mg/L发酵产物;在以db/db小鼠为模型的体内葡萄糖耐量实验中,MPL-2可有效促进小鼠胰岛素第一时相(5~15min)分泌,显著提高小鼠的葡萄糖耐受能力。在MPL-2的长效药效学实验中,经过8周连续用药治疗后,MPL-2可显著提高db/db小鼠的胰岛素敏感性,胰岛素耐量实验60min时MPL-2可将小鼠血糖降至初始值的63.52%;同时,在8周连续用药治疗过程中,与生理盐水(NS)处理组相比,MPL-2可有效降低db/db小鼠的体重、空腹血糖、饮食量、饮水量,分别低于NS组21.98%、21.46%、22.20%、60.07%,而且可显著改善db/db小鼠的血脂常数,生物学作用显著优于多肽BAY55-9837。建立了新型基因重组PACAP27衍生多肽MPL-2的高效制备技术,重组多肽MPL-2可有效改善2型糖尿病db/db小鼠的葡萄糖耐量、胰岛素敏感性、血脂常数,显著降低db/db小鼠的体重、空腹血糖、饮食和饮水量,从而发挥治疗2型糖尿病的生物学作用,可为MPL-2的药用研发提供实验数据。     

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.     

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。     

白茶对糖尿病模型小鼠降血糖作用的研究

目的：研究不同原料来源白茶的降血糖效果及机理。方法：以黄大茶水提物作为参比,探究白毫银针、白牡丹及寿眉水提物对高脂高糖饲料结合链脲霉菌素注射致糖尿病模型小鼠的血糖、葡萄糖耐量、HOMA稳态模型及血清转氨酶的影响,并用qPCR测定小鼠肝脏中糖代谢相关基因的表达水平。结果：白毫银针、白牡丹、寿眉及黄大茶水提物均具有降低小鼠血糖的功效,其血糖下降率分别为21.7%、27.3%、34.8%和25.1%,并且均可增加小鼠糖耐量,改善HOMA。四种茶叶水提物均使TXNIP和Foxo1的表达量下调,寿眉水提物显著上调GLUT4的表达量。结论：三种白茶均对糖尿病有一定治疗作用,其中多叶型茶寿眉降糖作用最为明显。 白茶;糖尿病小鼠;降血糖     

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。     

海参肽对db/db小鼠降糖作用和炎症反应程度的影响

目的：观察海参肽对2型糖尿病模型小鼠的降糖作用和炎症反应程度的影响作用,为海参肽在糖尿病降糖作用以及抗炎作用提供科学依据。方法：本研究拟以海参肽为干预物,以db/db小鼠为模型动物开展研究。选用空腹血糖水平≥11.1mmol/L的db/db小鼠,适应饲养1w后,以不同浓度的海参肽连续灌胃45d,期间观察其毛色、活动情况以及饮水排尿量,并于实验前、中、后期测定空腹血糖,实验前后期进行口服葡萄糖耐量实验,实验后采血测定相关血液生化指标,通过组间比较以判定海参肽的作用。结果：和模型对照组相比,海参肽中、高剂量组均能不同程度地改善2型糖尿病小鼠的体征状况,减轻多饮、多食、多尿的“三多”症状,提高2型糖尿病小鼠的生活质量。干预期间的同组横向对比中,中、高剂量海参肽干预组能够明显地降低db/db小鼠的空腹血糖（P＜0.05）,干预2、4、6w后,血糖值分别由13.62±1.64mmol/L降至11.59±3.26mmol/L,由14.82±3.09mmol/L降至12.36±3.28mmol/L;口服葡萄糖耐量实验中,在干预6w后,中、高剂量海参肽能有效降低db/db小鼠给予葡萄糖前后各时间点的血糖值和血糖—时间曲线下面积（P＜0.05）。在炎症抑制方面,与模型对照组相比,海参肽中、高剂量组能够显著降低IL-6、IL-8在小鼠体内的含量（P＜0.05）,提高IL-10在小鼠体内的表达（P＜0.05）,同时海参肽中、高剂量组能够降低TGF-α、MCP-1在小鼠体内的表达,从而具有一定的抗癌作用。结论：海参肽能够有效改善db/db小鼠的血糖调节能力以及口服糖耐量调节能力,同时发现海参肽可以有效抑制db/db小鼠体内炎症反应水平,一定程度上为海参肽于2型糖尿病防治及2型糖尿病并发炎症领域的应用及合理开发提供了新的思路和理论基础。     

Ginseng berry reduces blood glucose and body weight in db/db mice.

In this study, we observed anti-diabetic and anti-obesity effects of Panax ginseng berry in adult C57BL/Ks db/db mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract at 150 mg/kg body wt. for 12 consecutive days. On Day 5, the extract-treated db/db mice had significantly lower fasting blood glucose levels as compared to vehicle-treated mice (180.5+/-10.2 mg/dl vs. 226.0+/-15.3 mg/dl, P < 0.01). On day 12, the extract-treated db/db mice were normoglycemic (134.3+/-7.3 mg/dl) as compared to vehicle-treated mice (254.8+/-24.1 mg/dl; P < 0.01). Fasting blood glucose levels of lean mice did not decrease significantly after treatment with extract. After 12 days of treatment with the extract, glucose tolerance increased significantly, and overall blood glucose exposure calculated as area under the curve (AUC) decreased 53.4% (P < 0.01) in db/db mice. Furthermore, db/db mice treated with extract (150 mg/kg body wt.) showed weight loss from 51.0+/-1.9 g on Day 0, to 46.6+/-1.7 g on Day 5, and to 45.2+/-1.4 g on Day 12 (P < 0.05 and P < 0.01 compared to Day 0, respectively). The body weight of lean littermates also decreased at the same dose of extract. These data suggest that Panax ginseng berry extract may have therapeutic value in treating diabetic and obese patients.     

Anti-hyperglycemic compound (GII) from fenugreek (Trigonella foenum-graecum Linn.) seeds, its purification and effect in diabetes mellitus

An anti-hyperglycemic compound named GII was purified from the water extract of the seeds of fenugreek (T. foenum-graecum) and shown to be different from trigonelline and nicotinic acid isolated earlier from the same plant. GII (50 mg/kg body weight, po) reduced blood glucose in glucose tolerance test (GTT) in the sub-diabetic and moderately diabetic rabbits and significantly reduced the area under the curve (AUC) of GTT. Treatment for 7 days of the sub-diabetic rabbits with GII (50 mg/kg body weight, po) improved glucose tolerance without reducing fasting blood glucose (FBG) which was nearly normal. The results suggest that there is no risk of hypoglycemia in near normal animals (may be humans also) with abnormal GTT. Treatment of the moderately diabetic rabbits with GII (100 mg/kg body weight for 3 weeks) reduced FBG to nearly normal value and improved GTT. GII was more effective than the standard drug tolbutamide. Intermittent therapy given on days 1-5, 11-15, 26-30 and 56-60 to moderately diabetic rabbits leaving in between days without treatment brought down FBG to normal and AUC during GTT was normal. After 15 days treatment with GII (100 mg/kg body weight for 3 weeks) glycosylated hemoglobin came down and insulin increased to normal values in the sub-diabetic, moderately diabetic and severely diabetic rabbits. GII treatment (100 mg/kg body weight for 15 days) brought down all the altered serum lipids (TC, HDLC, TAG, PLs and FFAs) to normal levels. The results suggest that intermittent therapy, instead of daily therapy is possible and GII has good potential as an oral anti-diabetic drug with intermittent therapy.     

Protective effect of Morus rubra L. leaf extract on diet-induced atherosclerosis in diabetic rats

The antiatherosclerotic effect of aqueous leaves extract of Morus rubra was studied in streptozotocin-induced diabetic rats fed with atherosclerotic (Ath) diet [1.5 ml olive oil containing 8 mg (3, 20,000 IU) vitamin D2 and 40 mg cholesterol] for 5 consecutive days. A short-term toxicity assessment was also conducted in healthy rats to examine toxic effects of the extract. Oral administration of extract to diabetic rats (100, 200 and 400 mg/kg body weight per day for a period of 30 days) produced significant (p<0.001) fall in fasting blood glucose (FBG) in a dose-dependent manner. Treatment with the extract (400 mg/kg) showed significant (p<0.001) improvement in body weight and serum lipid profile i.e., total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol, when compared with diabetic control. Endothelial dysfunction parameters (sVCAM-1, Fibrinogen, total NO levels and oxidized LDL), apolipoprotein A and apolipoprotein B were significantly (p<0.001) reversed to near normal, following treatment with the extract. Thus, our study shows that aqueous leaf extract of Morus rubra (400 mg/kg) significantly improves the homeostasis of glucose and fat and possesses significant anti-atherosclerotic activity.     

Anti-diabetic effects of electrolyzed reduced water in streptozotocin-induced and genetic diabetic mice

Oxidative stress is produced under diabetic conditions and is likely involved in progression of pancreatic beta-cell dysfunction found in diabetes. Both an increase in reactive oxygen free radical species (ROS) and a decrease in the antioxidant defense mechanism lead to the increase in oxidative stress in diabetes. Electrolyzed reduced water (ERW) with ROS scavenging ability may have a potential effect on diabetic animals, a model for high oxidative stress. Therefore, the present study examined the possible anti-diabetic effect of ERW in two different diabetic animal models. The genetically diabetic mouse strain C57BL/6J-db/db (db/db) and streptozotocin (STZ)-induced diabetic mouse were used as insulin deficient type 1 and insulin resistant type 2 animal model, respectively. ERW, provided as a drinking water, significantly reduced the blood glucose concentration and improved glucose tolerance in both animal models. However, ERW fail to affect blood insulin levels in STZ-diabetic mice whereas blood insulin level was markedly increased in genetically diabetic db/db mice. This improved blood glucose control could result from enhanced insulin sensitivity, as well as increased insulin release. The present data suggest that ERW may function as an orally effective anti-diabetic agent and merit further studies on its precise mechanism.     

Antidiabetic effect of Cogent db,a herbal drug in alloxan-induced diabetes mellitus

Cogent db, a compound herbal drug, was investigated for its possible antidiabetic effect in alloxan-induced diabetic rats. Oral administration of 0.15, 0.30 and 0.45 g/kg body wt. of the aqueous solution of Cogent db for 40 days exhibited a significant reduction in blood glucose, glycosylated haemoglobin and increased plasma insulin, total haemoglobin along with antihyperlipidemic effects in diabetic rats. The effective dose was found to be 0.45 g/kg body wt. It also prevents body weight loss in diabetic rats. An oral glucose tolerance test (OGTT) was also performed in experimental diabetic rats in which there was a significant improvement in glucose tolerance in rats treated with Cogent db. A comparison was made between the action of Cogent db and a known antidiabetic drug — glibenclamide (600 μg/kg body wt.). The antidiabetic effect of Cogent db was more effective than that observed with glibenclamide.     

Treatment of type 2 diabetic db/db mice with a novel PPARgamma agonist improves cardiac metabolism but not contractile function

Hearts from insulin-resistant type 2 diabetic db/db mice exhibit features of a diabetic cardiomyopathy with altered metabolism of exogenous substrates and reduced contractile performance. Therefore, the effect of chronic oral administration of 2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid (COOH), a novel ligand for peroxisome proliferator-activated receptor-gamma that produces insulin sensitization, to db/db mice (30 mg/kg for 6 wk) on cardiac function was assessed. COOH treatment reduced blood glucose from 27 mM in untreated db/db mice to a normal level of 10 mM. Insulin-stimulated glucose uptake was enhanced in cardiomyocytes from COOH-treated db/db hearts. Working perfused hearts from COOH-treated db/db mice demonstrated metabolic changes with enhanced glucose oxidation and decreased palmitate oxidation. However, COOH treatment did not improve contractile performance assessed with ex vivo perfused hearts and in vivo by echocardiography. The reduced outward K+ currents in diabetic cardiomyocytes were still attenuated after COOH. Metabolic changes in COOH-treated db/db hearts are most likely indirect, secondary to changes in supply of exogenous substrates in vivo and insulin sensitization.     

Antihyperglycemic activity of Tarralin™, an ethanolic extract of Artemisia dracunculus L.

The studies reported here were undertaken to examine the antihyperglycemic activity of an ethanolic extract of Artemisia dracunculus L., called Tarralin in diabetic and non-diabetic animals. In genetically diabetic KK-A(gamma) mice, Tarralin treatment by gavage (500 mg/kg body wt./day for 7 days) lowered elevated blood glucose levels by 24% from 479+/-25 to 352+/-16 mg/dl relative to control animals. In comparison, treatment with the known antidiabetic drugs, troglitazone (30 mg/kg body wt./day) and metformin (300 mg/kg body wt./day), decreased blood glucose concentrations by 28% and 41%, respectively. Blood insulin concentrations were reduced in the KK-A(gamma) mice by 33% with Tarralin, 48% with troglitazone and 52% with metformin. In (STZ)-induced diabetic mice, Tarralin treatment, (500 mg/kg body wt./day for 7 days), also significantly lowered blood glucose concentrations, by 20%, from 429+/-41 to 376+/-58 mg/dl relative to control. As a possible mechanism, Tarralin was shown to significantly decrease phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression by 28% in STZ-induced diabetic rats. In non-diabetic animals, treatment with Tarralin did not significantly alter PEPCK expression, blood glucose or insulin concentrations. The extract was also shown to increase the binding of glucagon-like peptide (GLP-1) to its receptor in vitro. These results indicate that Tarralin has antihyperglycemic activity and a potential role in the management of diabetic states.     

Antidiabetic activity of Taxus cuspidata polysaccharides in streptozotocin-induced diabetic mice

In present study, crude polysaccharides (TCPs) were obtained by hot water extraction and ethanol precipitation from the Taxus cuspidata. With a purpose of finding valuable and economical drug for diabetes, TCPs was administered orally at three doses [50, 100 and 200 mg/kg body weight (b.w.)] to the diabetic mice induced by streptozotocin (STZ). The body weight, fasting blood glucose (FBG), fasting serum insulin (FINS), lipid peroxidation and superoxide dismutase (SOD) activity, as well as glucose tolerance were evaluated in normal and STZ-induced diabetic mice. TCPs could dose-dependently significantly increase the body weight of diabetic mice, and reverse the decrease of SOD and the increase of thiobarbituric acid reactive substances (TBARS) in kidney and liver of diabetic mice as compared to those in control group. Meanwhile, the level of FBG markedly decreased in diabetic mice administrated with TCPs, followed by the enhancement of FINS level especially at the higher dose. Furthermore, glibenclamide and TCPs significantly suppressed the rise in blood glucose after 30 min in the acute glucose tolerance test. These results indicated that TCPs could be developed to a potential anti-diabetic drug in the future.