胰高血糖素样肽-1的研究进展

胰高血糖素样肽-1(GLP-1)是由远端回肠、直肠和结肠内分泌L细胞分泌的一种十分重要的肠促胰岛素,在调节体内葡萄糖稳态中起重要作用。其在胰腺内的主要生理学作用包括进食后刺激胰岛素的分泌和生物合成、促进胰腺β细胞的增殖、抑制其凋亡及抑制胰高血糖素的分泌。大量研究表明,在胰岛素作用的靶器官肝脏、骨骼肌和脂肪组织上亦存在高亲和力的GLP-1结合位点,GLP-1可促进肝脏、骨骼肌和脂肪组织的糖原合成和脂肪生成。此外,GLP-1受体还分布于神经、心血管、胃肠、肺脏组织等,其分布的广泛性也决定其作用的广泛性,具有多种生物学作用,这使得它成为一种治疗糖尿病的新型药物,具有很好的临床应用前景。近年来,人们对GLP-1在胰腺内、外的作用进行了广泛研究,现将其进展综述如下。     

胰高血糖素样肽1类似物的研究进展

主要介绍了胰高血糖素样肽-1(Glucagon—Like Peptide-1，GLP-1)类似物的研究进展以及临床应用情况，并指出了今后发展方向。     

胰高血糖素样肽-1研究概况

肠促胰素已成为治疗2型糖尿病的热点。胰高血糖素样肽-1具有促进胰岛素合成和分泌、抑制胰高血糖素分泌、促进胰岛B细胞增殖的生理功能。此外,胰高血糖素样肽。1还具有延缓胃排空、抑制食欲和调节脂肪代谢等功能。艾塞那肽和利拉鲁肽是目前临床应用较多的胰高血糖素样肽-1类似物,临床研究证实其能有效降低血糖、糖化血红蛋白水平及体重指数且无低血糖反应,为2型糖尿病患者治疗带来了新的希望。胰高血糖素样肽-1类似物也存在一定的不良反应,其长期安全性有待进一步观察研究。     

胰高血糖素样肽-1对糖尿病周围神经病变的影响

胰高血糖素样肽-1（Glucagon-like peptide-1,GLP-1）是肠道因进食而分泌的一类促胰岛素分泌肽,主要通过作用于GLP-1受体,激活多种信号通路而对神经系统发挥影响,主要包括加快神经传导速度,增加神经轴突的数量,为神经细胞直接提供营养因子,抑制神经细胞凋亡,拮抗氧化应激等作用。GLP-1及其受体激动剂可通过多种不同的途径改善糖尿病周围神经病变的症状,为糖尿病周围神经病变的治疗提供新的方法。     

胰高血糖素样肽1与糖尿病的治疗

胰高血糖素样肽1(glucagon-like peptide-1,GLP-1)是由肠道L细胞分泌的一种重要的肠促胰岛素激素,其在体内的主要生理作用有刺激胰岛素的分泌和释放、抑制胰高血糖素的分泌、促进胰腺β细胞的增殖并抑制其凋亡、抑制胃的排空、促进饱食感的产生等。GLP-1对糖尿病和肥胖具有很好的治疗前景。由于GLP-1在体内很快被二肽酰基肽酶Ⅳ降解,血浆半衰期很短,因而限制了其临床应用。现已发现了促进GLP-1分泌的物质,开发了多种GLP-1的衍生物和二肽酰基肽酶Ⅳ抑制剂,为开发新型糖尿病治疗药物开辟了新的天地。     

胰高血糖素样肽-1及其类似物的研究进展

目的介绍胰高血糖素样肽-1(GLP-1)及其类似物的结构特点、研究进展以及临床情况。方法查阅国内外文献及相关资料,根据GLP-1的结构特点,归纳了对其进行的结构改造与修饰的方法及所产生的临床药效。结果 GLP-1能葡萄糖浓度依赖地促进胰岛素分泌,能降低2型糖尿病患者糖化血红蛋白水平和餐后血糖,并能减轻体质量。结论通过对GLP-1的结构改造与修饰,开发更稳定更有效的GLP-1类似物,是未来糖尿病治疗领域的主要研究思路之一。     

胰高血糖素样肽-1及其类似物的心血管保护作用研究进展

胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)是一种主要由肠L细胞分泌的肠促胰素,在调节葡萄糖稳态中发挥重要作用,能够通过多种途径降低血糖,胰高血糖素样肽-1及其类似物已用于2型糖尿病治疗。研究发现GLP-1不仅具有降糖作用,还可以通过减轻体重、改善血脂等心血管危险因素和针对心脏及血管的直接作用起到心血管保护效应。目前GLP-1对心血管的保护效应愈来愈受到关注,本文就近年来有关GLP-1及其类似物的心血管保护作用及机制的研究进展做一综述。     

胰高血糖素样肽-1受体激动剂研究进展

胰高血糖素样肽-1(GLP-1)是一种肠促胰岛素分泌剂,在维持人体血糖稳定中发挥着重要作用。与目前临床使用的药物相比,胰高血糖素样肽-1受体激动剂(GLP-1RA)在治疗2型糖尿病(T2DM)中显示出更好的应用前景,低血糖风险低,不会导致体重增加。但是,由于人体自身GLP-1的半衰期很短(约2 min),容易被二肽基肽酶-4(DPP-4)降解,这限制了它在糖尿病治疗领域的应用。本文梳理了具有抗DPP-4酶活性的GLP-1RA,如艾塞那肽、利拉鲁肽、索马鲁肽、度拉鲁肽、利司那肽等已上市产品的概况。另外还汇总了GLP-1RA在中国以及美国用药指南中的变化。近年,随着对GLP-1RA认识的逐步深入,GLP-1RA在T2DM治疗中的地位稳步提升。未来,随着GLP-1RA口服制剂的开发,GLP-1RA与胰岛素、GLP-1RA与其他激素的联合应用,都将使GLP-1RA在T2DM治疗中发挥更大的作用。     

胰高血糖素样肽

哺乳类胰高血糖素前体基因编码两种胰高血糖素样肽(GL Ps) ,胰高血糖素样肽 - 1(GL P- 1)和胰高血糖素样肽- 2 (GL P- 2 ) ,它们大约 5 0 %的氨基酸与胰腺的胰高血糖素(Gg)相同。Gg、GL P- 1和 GL P- 2的生物活性 ,从多水平调节营养物质的吸收和能量的内环境稳定。 GL P- 1和 GL P-2对糖尿病和肠机能障碍实验模型发挥多方面有意义的作用 ,因此这些肽分别在人类疾病治疗的临床实验被评价。1　 GL P- 1和 GL P- 2的合成、分泌和降解胰高血糖素前体在胰岛 A细胞中的加工处理主要产生含有 2 9个氨基酸的 Gg和未处理的主要胰高血糖…     

胰高血糖素样肽-1及类似物的降压作用研究进展

胰高血糖素样肽-1是体内一种重要的肠促胰岛素,具有葡萄糖浓度依赖性降糖作用,其类似物已用于2型糖尿病治疗。近年来的临床前和临床研究均发现胰高血糖素样肽-1及类似物有一定程度的降压作用,其作用机制可能与促进水钠排泄、改善血管内皮功能等有关。本文综述胰高血糖素样肽-1及类似物的降压作用。     

Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats

Diabetes mellitus is characterized by hyperglycemia and complications affecting the eye, kidney, nerve and blood vessel. We have previously demonstrated the occurrence of oxidative stress of streptozotocin-induced diabetic rats, preceded by a depletion in the tissue level of glutathione. In this study, when diabetic rats were treated with ginsenoside Re of Panax ginseng C.A. Meyer, there was a significant reduction in blood glucose, total cholesterol and triglyceride levels. On the other hand, oxidative stress has been implicated in the pathogenesis of diabetes and its complications. It was found that treatment by ginsenoside Re restored the levels of both glutathione and malondialdehyde in the eye and kidney to those found in the control rats. This is the first report demonstrating ginsenoside Re has significant antioxidant efficacy in diabetes, and prevents the onset of oxidative stress in some vascular tissues. Our results demonstrated that ginsenoside Re could lower blood glucose and lipid levels, and exerts protective actions against the occurrence of oxidative stress in the eye and kidney of diabetic rats. Our data also provide evidence that ginsenoside Re could be used as an effective antidiabetic agent particularly in the prevention of diabetic microvasculopathy.     

胰岛素样生长因子-1与糖尿病大鼠肾脏病变的关系

目的:探讨胰岛素样生长因子-1(IGF-1)与糖尿病大鼠肾脏病变的关系.方法:观察链脲佐菌素(STZ)糖尿病大鼠6、10、14周空腹血糖(VBG)、血清IGF-1,24h尿白蛋白排泄率(UAER)及肾脏的病理变化,用免疫组化方法检测肾脏IGF-的表达.结果:实验组大鼠随着病程的延长,血清IGF-1较对照组显著下降,与对照组比较差异有统计学意义(P<0.01);免疫组化半定量分析显示,实验组大鼠肾组织IGF-1的表达较对照组升高,并随着病程的延长有下降趋势,差异有显著性.结论:肾组织IGF-1与糖尿病肾脏病变发生显著相关.提示IGF-1参与了DN的发生发展,其中IGF-1可能发挥保护性作用.     

阿托伐他汀对糖尿病大鼠大血管组织单核细胞趋化蛋白1表达的影响

目的 研究链脲佐菌素(STZ)诱导的糖尿病(DM)大鼠大血管组织中单核细胞趋化蛋白1(MCP-1)的表达和阿托伐他汀对MCP-1表达的影响.方法 30只SD大鼠随机分成正常对照(NC)组和DM造模组,造模组给予STZ 60 mg/kg一次性腹腔注射,造模成功后再随机分为DM组和DM 阿托伐他汀治疗(AT)组,AT组大鼠给予阿托伐他汀(15 mg·kg-1·d-1)灌胃.于8周末,1%戊巴比妥麻醉下取胸主动脉,分别采用半定量RT-PCR及Western blot方法检测大血管组织中MCP-1 mRNA和蛋白的表达水平.结果 与DM组相比,AT组大鼠体重、血糖水平无明显差异(P＞0.05),而血浆胆固醇、甘油三酯明显降低(P＜0.05).与NC组相比,DM组大鼠大血管组织MCP-1 mRNA和蛋白的表达明显增加(P＜0.01);与DM组相比,AT组大鼠大血管组织MCP-1mRNA和蛋白的表达水平明显降低(P＜0.01).结论 糖尿病大鼠血管组织中MCP-1的表达明显升高,而阿托伐他汀可能通过减少炎症因子MCP-1的表达而对糖尿病大血管并发症产生治疗作用.     

Ginsenoside Re attenuates diabetes-associated cognitive deficits in rats

Objective

This study was designed to investigate the effect of ginsenoside Re (Re) on cognitive functions, oxidative stress and inflammation in streptozotocin-induced diabetic rats.

Research design and method

Diabetic rats were treated with Re (40 mg/kg) for 8 weeks, blood glucose and body weight were measured monthly and weekly, respectively. Cognitive performances were evaluated with Morris water maze. Brain was obtained for measurements of TNF-α and malondialdehyde (MDA) contents in both temporal cortex and hippocampus, blood was collected for assays of TNF-α, MDA and reduced glutathione (GSH) levels.

Results

Learning and memory abilities were significantly (both P < 0.01) impaired in diabetic rats, accompanied by the marked (all P < 0.01) elevations of TNF-α and MDA levels in temporal cortex and hippocampus. Increment of MDA and decrement of GSH in serum also occurred with significant differences (both P < 0.01). Chronic treatment with Re markedly (P < 0.05) improved the cognition of diabetic rats, evidenced by the decreased escape latency and the increased percentage of time spent in the target quadrant. Furthermore, Re treatment remarkably (P < 0.05) reduced the levels of TNF-α and MDA in both brain areas of diabetic rats. Decline of MDA level and elevation of GSH level in serum were also seen in Re-treated diabetic rats, coupled with decrease in serum glucose level, all with statistically significant differences.

Conclusions

Our findings firstly provide the first evidence that ginsenoside Re can remarkably attenuate diabetes-associated cognitive decline, secondly confirm the involvement of oxidative stress and inflammation in the development of cognitive impairment caused by diabetes, finally point toward the potential of ginsenoside Re as an adjuvant therapy to conventional anti-hyperglycemic regimens as well as diabetes-associated cognitive decline.     

HPLC法测定益心复脉颗粒中人参皂苷Rg_1、Re、Rb_1的含量

目的:建立以高效液相色谱法测定益心复脉颗粒中人参皂苷Rg1、Re、Rb1含量的方法。方法:色谱柱为Diamond C18(150mm×4.6mm,5μm),流动相为乙腈-水(梯度洗脱),流速为1mL·min-1,检测波长为203nm,柱温为25℃,进样量为10μL。结果:人参皂苷Rg1、Re和Rb1分别在0.645～6.450μg(r=0.999 8)、0.54～5.40μg(r=0.999 7)和0.605～6.050μg(r=0.999 9)范围内与各自峰面积积分值呈良好线性关系;三者平均加样回收率分别为100.59%(RSD=2.03%)、98.70%(RSD=1.46%)和98.99%(RSD=1.19%)。结论:本方法灵敏度高、简便、准确,可用于益心复脉颗粒的质量控制。     

高效液相色谱法测定益心口服液中人参皂苷含量

目的建立测定益心口服液中人参皂苷Rg1和人参皂苷Re含量的高效液相色谱（HPLC）法。方法以十八烷基硅烷键合硅胶为填充剂,乙腈-水（20：80）为流动相,检测波长203nm,进样量20μL。结果人参皂苷Rgt质量浓度线性范围为83．5～1670．0μg／mL,回归方程Y=3007．4x＋1694．4,r=0．9997（n=6）;人参皂苷Re质量浓度线性范围为88．2～1764．0μg／mL,回归方程Y=2956．6X-3148．6,r=0．9999（n=6）。人参皂苷Rg1的平均回收率为100．27％,RSD为1．48％（n=9）;人参皂苷Re的平均回收率为100．79％,RSD为1．72％（n=9）。结论HPLC法测定益心口服液中人参皂苷Rg1和人参皂苷Re的含量,准确度高,重现性好,简便快速。     

西洋参中人参皂苷Rg1人参皂苷Re和人参皂苷Rb1的含量测定

［摘要］目的用快速分离液相色谱法分离测定西洋参中人参皂苷Rg1、人参皂苷Re和人参皂苷Rb1的含量。方法采用ZOBAX SB C18柱（4.6 mm×50 mm,1.8 μm）,流动相：乙腈（A） 0.1%磷酸（B）,梯度洗脱（0～25min,5%A→20%A;～35min,20%A→40%A）;流速：2.0 mL&#8226;min 1,测定波长：203 nm,柱温：35 ℃。结果人参皂苷Rg1、人参皂苷Re和人参皂苷Rb1的线性范围分别为0.12～2.49,0.61～12.15,1.42～28.48 μg,相关系数分别为0.999 8,0.999 6,0.999 9;平均加样回收率（n=6）分别为97.8%,98.1%,98.3%;RSD分别为1.0%,0.8%,0.4%。结论该方法具有快速、准确、重复性好等特点,适合于西洋参的含量测定。     

凯时治疗糖尿病性周围神经病变50例疗效观察

目的 观察凯时注射液对糖尿病周围神经病变(DPN)的治疗效果。方法 对50例确诊为DPN的患者予凯时注射液10μg/d(加入莫菲氏管内滴入)共2周。结果 注射2周后症状和体征即改善,改善率分别为95.0％(下肢自发痛),94.1％(上肢自发痛),90.5％(感觉减退),94.5％(麻木),77.7％(发冷),57.1％(发热);患者治疗前MCV和SCV均明显下降,以下肢更为显著,经治疗后有一定改善(P<0.05)。结论 凯时是治疗DPN的一种安全、有效的药物。     

Hypoglycaemic effect of Melothria heterophylla in streptozotocin-induced diabetic rats

Context: In the Indian traditional system of medicine, Melothria heterophylla (Lour.) Cogn., (Cucurbitaceae) is prescribed for the treatment of diabetes mellitus.

Objective: In the present study, the antidiabetic effect of ethanol extract of Melothria heterophylla (EEMH), and its active isolated constituents were investigated in streptozotocin (STZ)-induced diabetic Swiss albino rats.

Method: Successive Soxhlet extraction of the dried total aerial parts with petroleum ether for defatting and then with ethanol (95%) to obtain ethanol extract, which was concentrated under reduced pressure. Hyperglycemia was induced in rats by STZ (50 mg/kg, body weight). Twenty-four hours after STZ induction, respective groups of diabetic rats received EEMH (200 and 400 mg/kg, body weight), gallic acid (GA) (2 and 4 mg/kg, body weight), and rutin (RU) (2 and 4 mg/kg, body weight), respectively, orally daily for 15 days. Glibenclamide (0.5 mg/kg, orally) served as reference. Blood glucose levels and change in body weight were measured on every 5^th day during 15 days of treatment. Biochemical parameters, viz., serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and serum insulin, were measured.

Results: EEMH and its active constituents significantly (p < 0.01) normalized blood glucose levels and serum biochemical parameters as compared to those of STZ controls. Both GA (4 mg/kg) and RU (4 mg/kg) exhibited maximum glucose lowering effect (69.1 and 66.7%, respectively) in diabetic rats compared to the other dose (2 mg/kg) at the end of the study. EEMH, gallic acid and RU also showed significant increase in serum insulin, and body weight of STZ-induced diabetic rats.

Conclusion: Therefore, ethanol extract of Melothria heterophylla, GA and RU demonstrated remarkable antidiabetic activity in STZ-induced diabetic rats.     

糖肝煎对2型糖尿病大鼠摄食及摄食抑制因子1、饥饿素的影响

目的 探究糖肝煎对2型糖尿病（T2DM）大鼠摄食及血浆摄食抑制因子1(Nesfatin-1)、饥饿素（Ghrelin）的影响。方法将50只SD大鼠采用随机数字表法分成正常组、T2DM组、利格列汀组（50 mg/kg利格列汀）、低剂量组（2.8 g/kg糖肝煎）、高剂量组（5.6 g/kg糖肝煎）,10只/组;通过尾静脉注射链脲佐菌素（STZ）及高脂饲料进行T2DM大鼠模型构建;利格列汀组、低剂量组及高剂量组连续4周给予相应药物灌胃,正常组及T2DM组给予等量生理盐水,1次/天,于实验结束后观察大鼠一般情况,并称取大鼠体质量,测定摄食量、摄水量、尿量;全自动生化分析仪测定大鼠血清空腹血糖（FBG）、低密度脂蛋白胆固醇（LDLC）、高密度脂蛋白胆固醇（HDL-C）、三酰甘油（TG）及总胆固醇（TC）水平;计算大鼠口服葡萄糖耐量试验（OGTT）曲线下面积（AUC）;酶联免疫吸附试验（ELISA）检测血清胰岛素（INS）水平及血浆核连蛋白2(NUCB2)、Ghrelin、Nesfatin-1水平;实时荧光定量逆转录聚合酶链式反应（qRT-PCR）检测血浆Nesfatin-1、Ghrelin m...