浅析磷酸西格列汀联合二甲双胍治疗新诊断2型糖尿病的降糖效果

目的探讨磷酸西格列汀联合二甲双胍治疗新诊断2型糖尿.病的降糖效果及对胰岛功能的保护作用。方法将2015年12月—2016年12月在广州市增城区人民医院内分泌科治疗的66例新诊断2型糖尿病患者随机分为两组,对照组单服二甲双胍治疗,观察组采用磷酸西格列汀联合二甲双胍治疗,比较两组患者的血糖及胰岛素功能。结果观察组治疗后FPG、2h PG、Hb A1c明显较对照组改善,差异有统计学意义(P<0.05);观察组治疗后HOMA-β、HOMAIR、IAI、血清APN明显较对照组改善,差异有统计学意义(P<0.05)。结论磷酸西格列汀联合二甲双胍治疗新诊断2型糖尿病效果显著,有利于血糖的平稳控制,延缓胰岛功能恶化,保护胰岛β细胞功能,具有积极的临床意义。     

锗—132对体外幼鼠胰岛细胞的作用

自1968年浅井等人[1]首次合成了乙基锗倍半氧化物（即Ge-132）以来，对Ge-132生物活性的研究已有诸多报道[2]．近年来，日本学者[3]在研究Ge-132药物活性作用机理时认为，Ge-132有可能成为防治糖尿病及其并发症的有效药物．但还没能从分子水平来阐明有机锗的作用机理．为揭示上述作用的细胞学机制，我们观察了Ge-132及Ge2。对体外培养的幼鼠胰岛细胞结构和功能的影响，比较了两者的差异．认为一定浓度的Ge-132对体外培养的幼鼠胰岛细胞分泌胰岛素具有明显的促进作用，为开发利用有机锗药物治疗糖尿病及其并发症提供了重要的依据．一周龄…     

低剂量三氯化钐对实验性非胰岛素依赖型糖尿病大鼠胰岛的影响

观察了经腹腔注射低剂量三氯化钐（０．０５ｍｇ／ｋｇ）对链脲佐菌素引志的非胰岛素依赖型糖尿病（ＮＤＩＤＤＭ）大鼠胰岛形态和功能的影响。结果表明，三氯化钐治疗组糖耐量改善、血清胰岛水平长高、血清胰镐血糖素水平降低、平均单个胰岛面积和胰岛β细胞数量明显增多，肝细胞内糖原含量增多。提示低剂量三氯化钐对实验性ＮＩＤＤＭ大鼠有一定的治疗作用。     

外泌体在糖尿病治疗中的研究进展

糖尿病（DMs）是威胁人类健康的严重代谢性疾病,其发病机制尚未明确,致病原因颇多。现已有多种糖尿病治疗方案,如注射外源胰岛素、植物源性天然产物、干细胞疗法等,但均存在难以改善胰岛β细胞、生物利用度差、免疫排斥等问题,因此亟待开发更加安全有效的治疗方案。外泌体（Exosomes）作为一种细胞分泌的囊泡,含有细胞内所有重要物质,且参与细胞间信息与物质传递,随着间充质干细胞等糖尿病有效治疗方案的逐步问世,同时包含多类同类物质的外泌体在糖尿病治疗中的潜力也逐步凸显,其可以通过多种途径同时降糖的作用被报道。本文综述了近十几年外泌体在Ⅰ型糖尿病（T1DM）与Ⅱ型糖尿病（T2DM）中的治疗方案,并介绍了其分子机制与具体治疗作用,以便为促进外泌体治疗策略在临床中的落实和应用提供参考。     

低剂量氯化镨对体外培养大鼠胰岛β细胞分泌胰岛素的影响

以体外培养的大鼠胰岛细胞为对象，利用放射免疫检测技术，免疫组织化学技术及透射电镜观察低剂量PrCl3对胰岛β细胞分泌胰岛素功能的影响，当PrCl3浓度分别为0．01和0．1mmol.L^-1时，培养液中胰岛素含量及培养孔内β细胞数目明显高于对照组，对体外培养的大鼠胰岛β细胞分泌胰岛素具有促进作用。     

缬沙坦联合氨氯地平治疗社区老年原发性高血压合并糖尿病的临床效果及安全性

目的探究在治疗老年性原发性高血压合并糖尿病患者中采用缬沙坦联合氨氯地平治疗的效果以及术后安全性,评估其临床意义,为临床治疗做出指导。方法以天津市滨海新区杭州道街社区卫生服务中心2013年5月—2014年6月间收诊的80例原发性高血压合并糖尿病老年患者的临床资料作为研究对象,按治疗方式不同将患者分成氨氯地平合并缬沙坦组40例(实验组)和单纯缬沙坦组40例(对照组)。测定分析两组患者治疗后情况,包括患者血压水平变化、空腹血糖、饭后2 h血糖以及胰岛素等指标,记录治疗情况。结果治疗后实验组血压水平下降的程度优于对照组(P0.05)。实验组空腹血糖等指标对比对照组均具有显著优势(P0.05)。结论联合氨氯地平缬沙坦治疗高血压合并糖尿病患者在血压下降水平、血糖前后变化水平等方面明显优于单纯使用缬沙坦治疗,不良反应发生率低,值得临床推广使用。     

治疗Ⅱ型糖尿病的GLP-1受体激动剂及其高分子递送系统的研究进展

糖尿病是一种以慢性高血糖为特征的代谢性疾病。糖尿病患者又以Ⅱ型患者为主,Ⅱ型糖尿病患者占比超过90%。胰高血糖素样肽-1(GLP-1)是由肠道L细胞分泌的一种肽类激素,能够以葡萄糖浓度依赖方式作用于胰岛β细胞,促进胰岛素基因的转录,增加胰岛素的生物合成和分泌;然而,GLP-1极易被体内的二肽基肽酶Ⅳ(DPP-4)降解,其血浆半衰期不足2min,缺乏临床应用价值。为了延期体内作用,许多GLP-1受体激动剂被研究和开发。根据其体内半衰期的长短,这些GLP-1受体激动剂可以分为短效型和长效型。同时,研究者还以各类功能高分子材料为载体,发展了不同GLP-1受体激动剂的递送体系来延长药物体内作用时间,减少给药频率,提高患者的顺应性。本综述介绍了已获得临床批准的GLP-1受体激动剂以及基于它们的热致水凝胶等药物递送系统在治疗Ⅱ型糖尿病中的应用。     

葡萄糖敏感苯硼酸基高分子纳米药物传输体系

近年来,智能葡萄糖敏感自调式药物传递系统备受关注。这种智能药物释放系统能够模拟胰腺分泌胰岛素的生理模式而精准调控药物释放并控制血糖水平,在糖尿病治疗中具有良好的应用前景。其中,苯硼酸(PBA)功能化的葡萄糖敏感高分子纳米载体成为近年来的研究热点之一。该类材料具有体系稳定、可长期储存、可逆的葡萄糖敏感性能等优势。根据响应因素不同,葡萄糖敏感药物传递系统可分为pH响应、温度响应和光响应等类型。本文重点介绍了基于PBA的葡萄糖敏感高分子纳米药物载体的发展过程、性能和应用,并对该领域的发展前景进行了展望。     

格列美脲与二甲双胍联合短期内强化治疗初诊2型糖尿病的疗效及安全性分析

目的 研究格列美脲与二甲双胍联合短期内强化治疗初诊2型糖尿病的疗效及安全性。方法 以天津市武清区河西务医院2015年1月—2016年11月初诊2型糖尿病患者106例随机分两组。A组采用常规饮食、运动等干预,并口服格列美脲治疗,B组在A组基础上联合二甲双胍治疗,共治疗12周。比较两组患者低血糖、肝肾和胃肠不良反应发生率;血糖达标时间;施行治疗前和施行治疗后患者血糖水平、胰岛素分泌指数、胰岛素抵抗指数的差异。结果 两组患者低血糖、肝肾和胃肠不良反应发生率无显著差异,P0.05;B组血糖达标时间短于A组,P0.05;施行治疗前两组血糖水平、胰岛素分泌指数、胰岛素抵抗指数比较无显著差异,P0.05;施行治疗后B组血糖水平、胰岛素分泌指数、胰岛素抵抗指数改善幅度更大,P0.05。结论格列美脲与二甲双胍联合短期内强化治疗初诊2型糖尿病的疗效及安全性高,可有效改善患者血糖水平和胰岛素分泌情况,低血糖风险低,安全可靠,值得推广。     

生物医用高分子在癌症药物治疗中的应用

利用生物医用高分子作载体,化学结合或物理包裹抗肿瘤化学药物、生物工程药物和放射药物,制剂通过植入或靶向运输至肿瘤区域。可增强药物在运输及吸收过程中的稳定性,提高药物的生物利用度,药物以一定速率从制剂中缓慢释放,可简化服用程序,在肿瘤区域维持较高的药物浓度,同时降低药物对全身的毒副作用。本文综述了生物医用高分子在高分子导向药物、抗肿瘤药物聚合物微球制剂,植入制剂以及肿瘤栓塞治疗中的应用。     

二价铜离子对人胰岛淀粉样蛋白(hIAPP)(11～28)多肽聚集的影响

人胰岛淀粉样蛋白(hIAPP)与Ⅱ型糖尿病(T2DM)密切相关,被认为是导致胰岛β细胞凋亡的致病因素之一,研究发现环境因素(如金属离子、pH值和温度等)对hIAPP的聚集过程有很大影响。本文采用多种生物物理的实验方法,研究了二价铜离子对hIAPP及其片段聚集的影响。原子力显微镜(AFM)和硫代黄素T(ThT)荧光的测量表明,铜离子能够明显地抑制hIAPP(11~28)聚集成纤维,其抑制程度随铜离子浓度的增加而明显加剧。显微傅里叶变换红外光谱(Micro-FTIR)的结果表明,铜离子能够抑制hIAPP多肽中α螺旋结构向β折叠的转变。另外,氨基酸定点突变实验结果表明,hIAPP(11~28)中的组氨酸(His18)可能对多肽的聚集行为和金属铜离子的相互作用起到了决定性的影响。     

Cucurbit[7]uril Inhibits Islet Amyloid Polypeptide Aggregation by Targeting N Terminus Hot Segments and Attenuates Cytotoxicity

Two “hot segments” within an islet amyloid polypeptide are responsible for its self-assembly, which in turn is linked to the decline of β-cells in type 2 diabetes (T2D). A readily available water-soluble, macrocyclic host, cucurbit[7]uril (CB[7]), effectively inhibits islet amyloid polypeptide (IAPP) aggregation through ion–dipole and hydrophobic interactions with different residues of the monomeric peptide in its random-coil conformation. A HSQC NMR study shows that CB[7] likely modulates IAPP self-assembly by interacting with and masking major residues present in the “hot segments” at the N terminus. CB[7] also prevents the formation of toxic oligomers and inhibits seed-catalyzed fibril proliferation. Importantly, CB[7] recovers rat insulinoma cells (RIN-m) from IAPP-assembly associated cytotoxicity.     

Folded Small Molecule Manipulation of Islet Amyloid Polypeptide

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Signaling mechanisms of glucose-induced F-actin remodeling in pancreatic islet β cells

The maintenance of whole-body glucose homeostasis is critical for survival, and is controlled by the coordination of multiple organs and endocrine systems. Pancreatic islet β cells secrete insulin in response to nutrient stimuli, and insulin then travels through the circulation promoting glucose uptake into insulin-responsive tissues such as liver, skeletal muscle and adipose. Many of the genes identified in human genome-wide association studies of diabetic individuals are directly associated with β cell survival and function, giving credence to the idea that β-cell dysfunction is central to the development of type 2 diabetes. As such, investigations into the mechanisms by which β cells sense glucose and secrete insulin in a regulated manner are a major focus of current diabetes research. In particular, recent discoveries of the detailed role and requirements for reorganization/remodeling of filamentous actin (F-actin) in the regulation of insulin release from the β cell have appeared at the forefront of islet function research, having lapsed in prior years due to technical limitations. Recent advances in live-cell imaging and specialized reagents have revealed localized F-actin remodeling to be a requisite for the normal biphasic pattern of nutrient-stimulated insulin secretion. This review will provide an historical look at the emergent focus on the role of the actin cytoskeleton and its regulation of insulin secretion, leading up to the cutting-edge research in progress in the field today.     

Molecular Mechanisms of Amylin Turnover,Misfolding and Toxicity in the Pancreas

Amyloidosis is a common pathological event in which proteins self-assemble into misfolded soluble and insoluble molecular forms, oligomers and fibrils that are often toxic to cells. Notably, aggregation-prone human islet amyloid polypeptide (hIAPP), or amylin, is a pancreatic hormone linked to islet β-cells demise in diabetics. The unifying mechanism by which amyloid proteins, including hIAPP, aggregate and kill cells is still matter of debate. The pathology of type-2 diabetes mellitus (T2DM) is characterized by extracellular and intracellular accumulation of toxic hIAPP species, soluble oligomers and insoluble fibrils in pancreatic human islets, eventually leading to loss of β-cell mass. This review focuses on molecular, biochemical and cell-biology studies exploring molecular mechanisms of hIAPP synthesis, trafficking and degradation in the pancreas. In addition to hIAPP turnover, the dynamics and the mechanisms of IAPP–membrane interactions; hIAPP aggregation and toxicity in vitro and in situ; and the regulatory role of diabetic factors, such as lipids and cholesterol, in these processes are also discussed.     

A High Cell‐Bearing Capacity Multibore Hollow Fiber Device for Macroencapsulation of Islets of Langerhans

Macroencapsulation of islets of Langerhans is a promising strategy for transplantation of insulin‐producing cells in the absence of immunosuppression to treat type 1 diabetes. Hollow fiber membranes are of interest there because they offer a large surface‐to‐volume ratio and can potentially be retrieved or refilled. However, current available fibers have limitations in exchange of nutrients, oxygen, and delivery of insulin potentially impacting graft survival. Here, multibore hollow fibers for islets encapsulation are designed and tested. They consist of seven bores and are prepared using nondegradable polymers with high mechanical stability and low cell adhesion properties. Human islets encapsulated there have a glucose induced insulin response (GIIS) similar to nonencapsulated islets. During 7 d of cell culture in vitro, the GIIS increases with graded doses of islets demonstrating the suitability of the microenvironment for islet survival. Moreover, first implantation studies in mice demonstrate device material biocompatibility with minimal tissue responses. Besides, formation of new blood vessels close to the implanted device is observed, an important requirement for maintaining islet viability and fast exchange of glucose and insulin. The results indicate that the developed fibers have high islet bearing capacity and can potentially be applied for a clinically applicable bioartificial pancreas.