哈佛大学研究人员研制新型激素造福糖尿病患者

哈佛大学干细胞研究所的PengYi等向小鼠注射胰岛素受体拮抗剂S961制造出胰岛素抗性模型,利用这个模型发现了与胰脏卢细胞增殖有关的激素,并命名为口．促激素（betatrophin）。     

干细胞研究的伦理学和社会学思考

每年都有千百万人罹患神经系统、心脏、肝脏和其他系统或器官的严重的和基本上无法治愈的变性疾病 ,例如神经系统的帕金森病或震颤麻痹、多发性硬化和中风 ,心脏的心肌梗死 ,肝脏的肝炎 ,胰脏的糖尿病等等 ,甚至最后死于这些疾病。干细胞疗法诚然有可能缓解甚或治愈某些上述疾病。然而 ,倘若这些干细胞来源于胚胎 ,那么对于这种干细胞疗法 ,在伦理学上又有什么看法呢 ?任何一种新的实验性医疗都可对医生和病人双方提出伦理学上的问题 ,但胚胎干细胞 (ＥＳ细胞 )研究则除此之外 ,还存在破坏性人类胚胎研究与可能的利益大小之间的伦理学矛盾。…     

饲料氧化鱼油对草鱼肝胰脏结构和功能的损伤

为了探讨饲料氧化鱼油对草鱼(Ctenopharyngodon idellus)肝胰脏组织结构及其功能的影响, 研究以豆油、鱼油及氧化鱼油作为饲料脂肪源, 分别设计鱼油组(6F)、豆油组(6S)、2%氧化鱼油(4S2OF)、4%氧化鱼油(2S4OF)及6%氧化鱼油(6OF)5组等氮、等能的半纯化饲料, 在池塘网箱中养殖72d。结果显示: 氧化鱼油显著增加草鱼血清ALB、GLB、MDA和GSH含量(P0.05), 显著降低肝胰脏GSH和SOD含量(P0.05); 氧化鱼油会显著增加草鱼肝胰脏指数及肝胰脏脂肪含量(P0.05), 且草鱼血清TG含量显著上升(P0.05), HDL/LDL显著下降(P0.05); 氧化鱼油使血清及肝胰脏TC含量显著增加(P0.05), 血清TBA显著下降(P0.05), 肝胰脏TBA显著上升(P0.05); 氧化鱼油会引起草鱼脂肪肝, 损伤肝胰脏细胞线粒体, 并导致肝胰脏细胞纤维化和组织萎缩。结果表明: 饲料添加氧化鱼油会引起草鱼氧化应激, 并降低草鱼肝胰脏抗氧化能力; 扰乱草鱼肝胰脏脂肪代谢, 引起脂肪肝; 影响胆汁酸肝肠循环, 使胆汁酸在肝胰脏中堆积, 并损伤肝胰脏细胞线粒体, 最终增加草鱼肝胰脏脂肪性肝炎发生率。     

牛蛙主要消化酶的分布及pH和温度对消化酶活力的影响

研究了牛蛙消化系统蛋白酶、脂肪酶、淀粉酶和纤维素酶的分布情况以及pH和温度对这些消化酶活力的影响.结果表明:在各自生理pH值下,牛蛙消化系统不同部位蛋白酶活力大小顺序依次为胰脏>胃>中肠>食道>前肠>后肠,胃、肠和胰脏蛋白酶的最适pH值分别为2.2、7.4和9.6,最适温度分别为45℃、50℃和45℃.脂肪酶活力大小顺序依次为胰脏>后肠>中肠>前肠>胃>食道,胃、肠和胰脏脂肪酶的最适pH值分别为2.2、7.4和8.0,最适温度均为50℃.淀粉酶活力大小顺序依次为胰脏>中肠>后肠>前肠>胃>食道,胃、肠道和胰脏淀粉酶的最适pH分别为7.0、8.0和9.6,最适温度均为35℃.在牛蛙消化系统未检测到明显纤维素酶活力.     

胰脏核糖核酸酶的生理功能和分子结构与进化

各种生物中广泛存在核糖核酸酶(RNase).自1939年Kunitz.首次得到结晶的牛胰脏RNase以来,生物化学家开始对动物胰脏RNase进行多方面的研究.首先是因为胰脏RNase是研究RNA结构的一种重要工具酶.其次,比较胰脏RNase分子中氨基酸的异同和性质,也是深入了解蛋白质结构与功能关系的重要手段,另外,研究进化地位不同的动物     

云斑尖塘鳢消化酶活力的研究

本文采用酶学分析方法研究了云斑尖塘鳢在正常摄食状态与饥饿的状态下胃、肠及肝胰脏组织中蛋白酶、淀粉酶和脂肪酶的活性。结果显示,在30℃的条件下,正常摄食组样本在酸性条件下的蛋白酶活力表现为:胃后肠肝胰脏前肠,中性和碱性条件下:后肠肝胰脏前肠及胃;饥饿组样本仅有胃表现出较高的酸性蛋白酶活性,其他器官的蛋白酶活性均很低。在正常和饥饿实验组中肝胰脏的淀粉酶活性均高于其他器官,胃肠的淀粉酶活性均较低。正常摄食组中脂肪酶活力后肠肝胰脏;而在饥饿组中仅有肝胰脏检测到脂肪酶活性。结果表明,云斑尖塘鳢适度饥饿组较正常摄食组消化酶活性大幅降低;其高蛋白酶活力及中等脂肪酶活力与其肉食性相一致;此外云斑尖塘鳢也具备少量的淀粉消化能力。     

草鱼、鲤、鲢、鳙和尼罗罗非鱼肝胰脏和肠道蛋白酶活性的初步探讨

草鱼、鲤、鲢、鳙肝胰脏和肠蛋白酶的最适pH值分别为8.7、8.7、7.6、7.6和8.4、8.7、8.0、8.4。草鱼、鲤和尼罗罗非鱼的肝胰脏蛋白酶活性比肠的高;鲢和鳙的肝胰脏蛋白酶的活性却比肠的低;尼罗罗非鱼胃的蛋白酶活性明显高于肝胰脏和肠的。草鱼、鲤和尼罗罗非鱼的肝胰脏蛋白酶活性明显高于鲢和鳙的;5种鱼的肠蛋白酶活性,鲤最高,尼罗罗非鱼最低,草鱼、鲢、鳙和尼罗罗非鱼间蛋白酶活性无明显差异。草鱼、鲤、鲢和尼罗罗非鱼的肠蛋白酶活性由前向后递减,而鳙的则以中肠活性最高。     

温度和pH对洞庭鲇鱼消化酶活性的影响

采用酶学分析方法研究了温度和pH对洞庭鲇鱼蛋白酶、脂肪酶和淀粉酶活力的影响。结果表明,在设定的温度和pH范围内,鲇鱼各消化酶的活力均随着温度和pH的升高呈现先升后降的变化趋势。其中,胃蛋白酶的最适温度为40℃,肝胰脏、前肠、中肠和后肠蛋白酶的最适温度为45℃;脂肪酶的最适温度均为35℃;胃淀粉酶的最适温度为35℃,其他部位均为30℃。胃、肝胰脏、前肠、中肠和后肠蛋白酶的适宜pH分别为2.0、8.5、7.5、8.0和8.0;脂肪酶的适宜pH均为7.5;淀粉酶肝胰脏的适宜pH为7.5,其余部位均为7.0。鲇鱼各消化酶活力存在器官特异性。在最适温度下,蛋白酶活力顺序为前肠>肝胰脏>胃>中肠>后肠,脂肪酶的活力顺序均为肝胰脏>胃>前肠>中肠>后肠,淀粉酶的活力顺序为肝胰脏>前肠>中肠>后肠>胃,各部位之间差异显著(P<0.05)。     

新发现的胰脏活性多肽

胰脏中除了人们所熟悉的胰岛素、胰高血糖素、生长激素释放抑制因子和胰多肽外,近几年又陆续发现了几个新的胰脏活性多肽。它们是甘丙肽(galanin),胰脏释放抑制因子(pancreastatin),胰岛淀粉样多肽(islet amyloid polypeptide)及胰岛素拮抗肽。本文着重介绍它们的结构与功能。对这些活性多肽的深入研究,无疑在理论上或临床实践中均将有其重要的意义。     

不同浓度阿维菌素对鲤鱼过氧化氢酶和谷胱甘肽-S-转移酶活性的影响

采用半静态水质接触染毒法,研究不同浓度(0、3.2、5.6、7.5、10.0和18.0μg.-1)阿维菌素对鲤鱼(Cyprinus carpio)肝胰脏和肌肉过氧化氢酶(CAT)、谷胱甘肽-S-转移酶(GSTs)活性的影响。结果表明:除3.2μg.L-1浓度对CAT和GSTs活性无显著影响外,其余各浓度的阿维菌素均对鲤鱼组织中CAT和GSTs产生显著影响,总体表现为低浓度诱导,高浓度先诱导后抑制;5.6和7.5μg.L-1浓度组的肌肉CAT活性与对照组相比无显著差异,肝胰脏CAT活性以及肌肉和肝胰脏GSTs活性均显著升高;10.0和18.0μg.L-1浓度组的肌肉和肝胰脏中CAT、GSTs活性先显著升高,随后又显著下降;解除污染胁迫10d,18.0μg.L-1浓度组的肝胰脏中酶活性不能恢复到正常水平,其余各组与对照无显著差异,说明高浓度阿维菌素暴露可能对鲤鱼机体造成不可逆损伤;阿维菌素暴露浓度与其对鲤鱼肝胰脏和肌肉CAT、GSTs活性抑制率之间具有显著的剂量-效应关系,可以考虑将其作为水体中阿维菌素类药物污染的生物标志物;同时,由于鲤鱼受污染胁迫时肌肉CAT、GSTs活性变化的显著性均远低于肝胰脏,因此当考虑...     

基质衍生因子(SDF-1)对骨髓间充质干细胞定向迁移的影响

目的:研究基质细胞衍生因子-1(SDF-1)/CXCR4轴在骨髓间充质干细胞迁徙到受损胰腺中的作用。方法:密度梯度离心、贴壁培养骨髓间充质干细胞,建立STZ诱导糖尿病模型并制备正常和受损胰腺组织提取液,利用Transwell小室体外迁移体系观察不同浓度SDF-1和不同组织提取液对骨髓间充质干细胞的趋化作用,及SDF-1/CXCR4特异抑制剂AMD3100对骨髓间充质干细胞迁移的影响。结果:成功培养了骨髓间充质干细胞并建立了糖尿病大鼠模型。SDF-l对骨髓间充质干细胞有剂量依赖性的趋化作用,造模1周的胰腺组织提取液对骨髓间充质干细胞有明显的趋化作用,而这种作用可部分被SDF-1受体CXCR4的抑制剂AMD3100抑制。结论:受损胰腺组织提取液对骨髓间充质干细胞有明显的趋化作用,SDF-1/CXCR4轴可能在组织提取液趋化骨髓间充质干细胞迁移中起主要的作用。     

Towards stem-cell therapy in the endocrine pancreas

Many approaches of stem-cell therapy for the treatment of diabetes have been described. One is the application of stem cells for replacement of nonfunctional islet cells in the native endogenous pancreas; another one is the use of stem cells as an inexhaustible source for islet-cell transplantation. During recent years three types of stem cells have been investigated: embryonic stem cells, bone-marrow-derived stem cells and organ-bound stem cells. We discuss the advantages and limitations of these different cell types. The applicability for the treatment of dysfunction of beta cells in the pancreas has been demonstrated for all three cell types, but more-detailed understanding of the sequence of events during differentiation is required to produce fully functional insulin-producing cells.     

Applications of stem cells and bioprinting for potential treatment of diabetes

Currently, there does not exist a strategy that can reduce diabetes and scientists are working towards a cure and innovative approaches by employing stem cellbased therapies. On the other hand, bioprinting technology is a novel therapeutic approach that aims to replace the diseased or lost β-cells, insulin-secreting cells in the pancreas, which can potentially regenerate damaged organs such as the pancreas. Stem cells have the ability to differentiate into various cell lines including insulinproducing cells. However, there are still barriers that hamper the successful differentiation of stem cells into β-cells. In this review, we focus on the potential applications of stem cell research and bioprinting that may be targeted towards replacing the β-cells in the pancreas and may offer approaches towards treatment of diabetes. This review emphasizes on the applicability of employing both stem cells and other cells in 3 D bioprinting to generate substitutes for diseased β-cells and recover lost pancreatic functions. The article then proceeds to discuss the overall research done in the field of stem cell-based bioprinting and provides future directions for improving the same for potential applications in diabetic research.     

Nestin-expressing cells in the pancreatic islets of Langerhans

The pancreatic islets of Langerhans produce several peptide hormones, predominantly the metabolically active hormones insulin and glucagon, which are critical for maintaining normal fuel homeostasis. Some evidence exists that pancreatic endocrine cells turn over at a slow rate and can regenerate in certain conditions. This could be due to the presence of pluripotent cells residing in the pancreas. Recently the intermediate filament protein nestin has been identified to be a marker for a multipotent stem cell in the central nervous system. Given the similarity between the pancreatic islets and neuronal cells, we hypothesized that stem cells expressing nestin might be present in the pancreas. Here we present evidence that a subset of cells in the pancreatic islets express the stem cell marker nestin. These cells might serve as precursors of differentiated pancreatic endocrine cells.     

Molecular pathways controlling pancreas induction

Recent advances in generating pancreatic cell types from human pluripotent stem cells has depended on our knowledge of the developmental processes that regulate pancreas development in vivo. The developmental events between gastrulation and formation of the embryonic pancreatic primordia are both rapid and dynamic and studies in frog, fish, chick, and mouse have identified the molecular basis of how the pancreas develops from multipotent endoderm progenitors. Here, we review the current status of our understanding of molecular mechanisms that control endoderm formation, endoderm patterning, and pancreas specification and highlight how these discoveries have allowed for the development of robust methods to generate pancreatic cells from human pluripotent stem cells.     

Nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas

Stem cell research and the prospect of stem cell based therapies depend critically on the identification of specific markers that can be used for the identification and selection of stem and progenitor cells. Nestin is expressed in neuronal progenitor cells and has also been suggested to mark multipotent pancreatic stem cells. We show here that, throughout pancreatic development, markers of pancreatic progenitor cells and differentiated pancreatic cells are expressed in E-cadherin-positive epithelial cells that do not express nestin. The data presented demonstrate that nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas.     

Chimeric mice reveal clonal development of pancreatic acini, but not islets

Intestinal crypt stem cells establish clonal descendants. To determine whether the pancreas is patterned by a similar process, we used embryonic stem (ES) cell chimeric mice, in which male ES cells were injected into female blastocysts. Fluorescence in situ hybridization for the Y chromosome (Y-FISH) revealed clonal patterning of ES-derived cells in the adult mouse small intestine and pancreas. Intestinal crypts were entirely male or entirely female. Villi contained columns of male or female epithelial cells, consistent with upward migration of cells from the crypts which surround them. Within the exocrine pancreas, acini were entirely male or entirely female, consistent with patterning from a single stem/progenitor cell. Pancreatic islets contained a mixture of male and female cells, consistent with patterning from multiple progenitors. Male-female chimeric mice demonstrate that the adult mouse exocrine pancreatic acinus is patterned from a single stem/progenitor cell, while the endocrine pancreas arises from multiple progenitors.     

Stem-cell-based approaches for regenerative medicine

Recent success in transplantation of islets raises the hopes of diabetic patients that replacement therapies may be a feasible treatment of their disease. Although several lines of evidence suggest that stem cells exist in the pancreas, it is still technically hard for us to isolate or maintain the stem cells in vitro. The establishment of human embryonic stem (ES) cells has excited scientists regarding their potential medical use in tissue replacement therapy. When applied with appropriate signals, ES cells can be directed to differentiate into a specific cell lineage. Therefore, ES cells are no doubt an excellent source not only for regenerative medicine but also for studies of early events of pancreatic development, and to portray the pancreatic progenitor cells. Despite many attempts that have been tried, the efficiency of differentiation of ES cells into islets is still very low. This low efficiency reflects our lack of understanding of the intrinsic and extrinsic signals which regulate the developmental processes of the pancreas. In this review, I present a summary of recent works on ES cells, the identification of pancreatic progenitor cells from the adult pancreas, and refer to the possibilities of transdifferentiation from adult stem cells derived from other tissues.     

Stem cell-based approaches to solving the problem of tissue supply for islet transplantation in type 1 diabetes

Type 1 diabetes is a debilitating condition, affecting millions worldwide, that is characterized by the autoimmune destruction of insulin-producing pancreatic islets of Langerhans. Although exogenous insulin administration has traditionally been the mode of treatment for this disease, recent advancements in the transplantation of donor-derived insulin-producing cells have provided new hope for a cure. However, in order for islet transplantation to become a widely used technique, an alternative source of cells must be identified to supplement the limited supply currently available from cadaveric donor organs. Stem cells represent a promising solution to this problem, and current research is being aimed at the creation of islet-endocrine tissue from these undifferentiated cells. This review presents a summary of the research to date involving stem cells and cell replacement therapy for type 1 diabetes. The potential for the differentiation of embryonic stem (ES) cells to islet phenotype is discussed, as well as the possibility of identifying and exploiting a pancreatic progenitor/stem cell from the adult pancreas. The possibility of creating new islets from adult stem cells derived from other tissues, or directly form other terminally differentiated cell types is also addressed. Finally, a model for the isolation and maturation of islets from the neonatal porcine pancreas is discussed as evidence for the existence of an islet precursor cell in the pancreas.     

Nestin expression in pancreatic stellate cells and angiogenic endothelial cells

Nestin is an intermediate filament protein expressed by neuroepithelial stem cells and which has been proposed to represent also a marker for putative islet stem cells. The aim of this study was to characterize the cell type(s) expressing nestin in the rat pancreas. By immunohistochemistry, nestin positivity was localized exclusively in mesenchymal cells of normal and regenerating adult pancreas. In the latter condition, the number of nestin-positive cells and the intensity of nestin immunoreactivity were greatly increased. Most nestin-positive cells had the morphology of stellate cells, a type of pericyte associated with blood vessels which has been previously reported to occur in liver and pancreas. In addition, nestin positivity was present in endothelial cells from neocapillaries during pancreas regeneration, and in all blood vessels during morphogenesis in fetal pancreas. Nestin expression was not found in the ductal epithelial cells from which islet cells originate in fetal and regenerating pancreas. In primary pancreatic tissue explants, nestin-positive mesenchymal cells rapidly attached to plastic and proliferated. These cells also expressed desmin, vimentin, and glial fibrillary acidic protein which are known to represent stellate cell markers. In summary, nestin in the pancreas is primarily a marker for reactive stellate cells, or pericytes, and endothelial cells during active angiogenesis.