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Pancreas islet

Kathrin Fielitz, Kristina Althoff, Katleen De Preter, Julie Nonnekens, Jasmin Ohli, Sandra Elges, Wolfgang Hartmann, Günter Klöppel, Thomas Knösel, Marc Schulte, Ludger Klein-Hitpass, Daniela Beisser, Henning Reis, Annette Eyking, Elke Cario, Johannes H Schulte, Alexander Schramm, Ulrich Schüller
Amplification or overexpression of MYCN is involved in development and maintenance of multiple malignancies. A subset of these tumors originates from neural precursors, including the most aggressive forms of the childhood tumors, neuroblastoma and medulloblastoma. In order to model the spectrum of MYCN-driven neoplasms in mice, we transgenically overexpressed MYCN under the control of the human GFAP-promoter that, among other targets, drives expression in neural progenitor cells. However, LSL-MYCN;hGFAP-Cre double transgenic mice did neither develop neural crest tumors nor tumors of the central nervous system, but presented with neuroendocrine tumors of the pancreas and, less frequently, the pituitary gland...
October 19, 2016: Oncotarget
G S M Paula, L L Souza, N O S Bressane, R Maravalhas, M Wilieman, T Bento-Bernardes, K R Silva, L S Mendonca, K J Oliveira, C C Pazos-Moura
Neuromedin B (NB) and gastrin-releasing peptide (GRP) are bombesin-like peptides, found in the gastrointestinal tube and pancreas, among other tissues. Consistent data proposed that GRP stimulates insulin secretion, acting directly in pancreatic cells or in the release of gastrointestinal hormones that are incretins. However, the role of NB remains unclear. We examined the glucose homeostasis in mice with deletion of NB receptor (NBR-KO). Female NBR-KO exhibited similar fasting basal glucose with lower insulinemia (48...
October 18, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Jamal Mohammadi Ayenehdeh, Bahareh Niknam, Seyed Mahmoud Hashemi, Hossein Rahavi, Nima Rezaei, Masoud Soleimani, Nader Tajik
BACKGROUND: Islet transplantation could be an ideal alternative treatment to insulin therapy for type 1 diabetes Mellitus (T1DM). This clinical and experimental field requires a model that covers problems such as requiring a large number of functional and viable islets, the optimal transplantation site, and the prevention of islet dispersion. Hence, the methods of choice for isolation of functional islets and transplantation are crucial. METHODS: The present study has introduced an experimental model that overcomes some critical issues in islet transplantation, including in situ pancreas perfusion by digestive enzymes through common bile duct...
October 18, 2016: Iranian Biomedical Journal
Maryam Kaviani, Negar Azarpira, Mohammad Hossein Karimi, Ismail Al-Abdullah
Cell-based therapies suggest novel treatments to overcome the complication of the current therapeutic approaches in diabetes mellitus type 1. Replacement of the destroyed pancreatic islet β-cells by appropriate alternative cells needs an efficient approach to differentiate the cells into viable and functional insulin producing cells. Small non-coding RNA molecules, MicroRNAs (miRNA), have critical roles in post-transcriptional regulation of gene expression. Therefore, they can direct the cells toward β-cell like cells and control islet β-cell development...
October 15, 2016: Cell Biology International
Masayuki Shimoda, Shinichi Matsumoto
Allogeneic islet transplantation has become a viable option for the treatment of unstable type 1 diabetes; however, donor shortage and the necessity for immunosuppressive drugs are two major drawbacks of this treatment. Microencapsulated porcine islets can solve both of these drawbacks, and clinical trials have been conducted. Previous clinical trials demonstrated the safety and marginal efficacy of this treatment; therefore, it is necessary to improve its efficacy. The production of microencapsulated porcine islets consists of pancreas procurement, islet isolation, and microencapsulation...
2017: Methods in Molecular Biology
Kevin Enck, John Patrick McQuilling, Giuseppe Orlando, Riccardo Tamburrini, Sittadjody Sivanandane, Emmanuel C Opara
Islet transplantation (IT) has recently been shown to be a promising alternative to pancreas transplantation for reversing diabetes. IT requires the isolation of the islets from the pancreas, and these islets can be used to fabricate a bio-artificial pancreas. Enzymatic digestion is the current gold standard procedure for islet isolation but has lingering concerns. One such concern is that it has been shown to damage the islets due to nonselective tissue digestion. This chapter provides a detailed description of a nonenzymatic method that we are exploring in our lab as an alternative to current enzymatic digestion procedures for islet isolation from human and nonhuman pancreatic tissues...
2017: Methods in Molecular Biology
William F Kendall, Emmanuel C Opara
Since the discovery of insulin by Banting and Best in 1921, the prognosis and treatment options for individuals with diabetes have improved. The development of various insulin types, various oral agents, and insulin pumps have improved the available medical options for individuals afflicted with diabetes. The current need for frequent blood glucose monitoring imposed by multiple daily insulin injections, result in significant life-style challenges for in individuals afflicted with Type 1 diabetes (T1D). In contrast the use of surgical interventions, such as whole organ pancreas transplantation (PT) requires less-intensive glucose monitoring while the organ is viable...
2017: Methods in Molecular Biology
Varna Sharma, Michael Hunckler, Melur K Ramasubramanian, Emmanuel C Opara, Kalyan C Katuri
Bioartificial pancreas made of insulin-secreting islets cells holds great promise in the treatment of individuals with Type-1 diabetes. Successful islet cell microencapsulation in biopolymers is a key step for providing immunoisolation of transplanted islet cells. Because of the variability in the size and shape of pancreatic islets, one of the main obstacles in their microencapsulation is the inability to consistently control shape, size, and microstructure of the encapsulating biopolymer capsule. In this chapter, we provide a detailed description of a microfluidic approach to islet cell encapsulation in alginate that might address the microencapsulation challenges...
2017: Methods in Molecular Biology
Yue J Wang, Maria L Golson, Jonathan Schug, Daniel Traum, Chengyang Liu, Kumar Vivek, Craig Dorrell, Ali Naji, Alvin C Powers, Kyong-Mi Chang, Markus Grompe, Klaus H Kaestner
The human endocrine pancreas consists of multiple cell types and plays a critical role in glucose homeostasis. Here, we apply mass cytometry technology to measure all major islet hormones, proliferative markers, and readouts of signaling pathways involved in proliferation at single-cell resolution. Using this innovative technology, we simultaneously examined baseline proliferation levels of all endocrine cell types from birth through adulthood, as well as in response to the mitogen harmine. High-dimensional analysis of our marker protein expression revealed three major clusters of beta cells within individuals...
October 11, 2016: Cell Metabolism
Cornelis R van der Torren, Jessica S Suwandi, DaHae Lee, Ernst-Jan T van 't Wout, Gaby Duinkerken, Godelieve Swings, Arend Mulder, Frans H J Claas, Zhidong Ling, Pieter Gillard, Bart Keymeulen, Peter In 't Veld, Bart O Roep
Transplantation of islet allografts into type 1 diabetic recipients usually requires multiple pancreas donors to achieve insulin independence. This adds to the challenges of immunological monitoring of islet transplantation currently relying on surrogate immune markers in peripheral blood. We investigated donor origin and infiltration of islets transplanted in the liver of a T1D patient who died of hemorrhagic stroke four months after successful transplantation with two intraportal islet grafts combining six donors...
October 10, 2016: Cell Transplantation
Diego Soares Carvalho, Marilia Melo Diniz, André Abour Haidar, Maria de Fátima Cavanal, Eduardo da Silva Alves, Angelo Rafael Carpinelli, Frida Zaladek Gil, Aparecida Emiko Hirata
Maternal hyperglycemia can result in defects in glucose metabolism and pancreatic β-cell function in offspring. The purpose of this study was to evaluate the impact of maternal diabetes mellitus on pancreatic islets, muscle and adipose tissue of the offspring, with or without oral l-Arginine supplementation. The induction of diabetes was performed using streptozotocin (60mg/kg). Animals were studied at 3 months of age and treatment (sucrose or l-Arginine) was administered from weaning. We observed that l-Arg improved insulin sensitivity in the offspring of diabetic mothers (DA), reflected by higher insulin-induced phosphorylation of Akt in muscle and adipose tissue...
October 4, 2016: European Journal of Pharmacology
Saba Parween, Elena Kostromina, Christoffer Nord, Maria Eriksson, Per Lindström, Ulf Ahlgren
The leptin deficient ob/ob mouse is a widely used model for studies on initial aspects of metabolic disturbances leading to type 2 diabetes, including insulin resistance and obesity. Although it is generally accepted that ob/ob mice display a dramatic increase in β-cell mass to compensate for increased insulin demand, the spatial and quantitative dynamics of β-cell mass distribution in this model has not been assessed by modern optical 3D imaging techniques. We applied optical projection tomography and ultramicroscopy imaging to extract information about individual islet β-cell volumes throughout the volume of ob/ob pancreas between 4 and 52 weeks of age...
October 7, 2016: Scientific Reports
Hong-Tu Li, Fang-Xu Jiang, Ping Shi, Tao Zhang, Xiao-Yu Liu, Xue-Wen Lin, Zhong-Yan San, Xi-Ning Pang
Islet transplantation provides curative treatments to patients with type 1 diabetes, but donor shortage restricts the broad use of this therapy. Thus, generation of alternative transplantable cell sources is intensively investigated worldwide. We previously showed that bone marrow-derived mesenchymal stem cells (bmMSCs) can be reprogrammed to pancreatic-like cells through simultaneously forced suppression of Rest/Nrsf (repressor element-1 silencing transcription factor/neuronal restrictive silencing factor) and Shh (sonic hedgehog) and activation of Pdx1 (pancreas and duodenal transcription factor 1)...
October 3, 2016: In Vitro Cellular & Developmental Biology. Animal
Toshiko Yamazawa, Naotoshi Nakamura, Mari Sato, Chikara Sato
Exocrine glands, e.g., salivary and pancreatic glands, play an important role in digestive enzyme secretion, while endocrine glands, e.g., pancreatic islets, secrete hormones that regulate blood glucose levels. The dysfunction of these secretory organs immediately leads to various diseases, such as diabetes or Sjögren's syndrome, by poorly understood mechanisms. Gland-related diseases have been studied by optical microscopy (OM), and at higher resolution by transmission electron microscopy (TEM) of Epon embedded samples, which necessitates hydrophobic sample pretreatment...
October 2, 2016: Microscopy Research and Technique
Nancy El-Hossary, Hamdy Hassanein, Abdel Wahab El-Ghareeb, Hisham Issa
AIM: To evaluate the efficiency of mesenchymal stem cells isolated from Wharton's jelly (WJ-MSCs) through either the intravenous or intraperitoneal transplantations into streptozotocin (STZ)-induced diabetic rats as a therapy for type 1 diabetes mellitus (T1DM). METHODOLOGY: A rat model with STZ induction was established and the rats were divided into 3 groups: a tail vein injection group, an intraperitoneal injection group and a STZ control group. Following transplantation, blood glucose levels were monitored weekly then the pancreatic tissues were collected to examine the pancreatic islets by histopathology and morphometric studies...
September 21, 2016: Diabetes Research and Clinical Practice
Mauro J Muraro, Gitanjali Dharmadhikari, Dominic Grün, Nathalie Groen, Tim Dielen, Erik Jansen, Leon van Gurp, Marten A Engelse, Francoise Carlotti, Eelco J P de Koning, Alexander van Oudenaarden
To understand organ function, it is important to have an inventory of its cell types and of their corresponding marker genes. This is a particularly challenging task for human tissues like the pancreas, because reliable markers are limited. Hence, transcriptome-wide studies are typically done on pooled islets of Langerhans, obscuring contributions from rare cell types and of potential subpopulations. To overcome this challenge, we developed an automated platform that uses FACS, robotics, and the CEL-Seq2 protocol to obtain the transcriptomes of thousands of single pancreatic cells from deceased organ donors, allowing in silico purification of all main pancreatic cell types...
September 29, 2016: Cell Systems
Xiaofang Bian, Clive Wasserfall, Garrick Wallstrom, Jie Wang, Haoyu Wang, Kristi Barker, Desmond Schatz, Mark Atkinson, Ji Qiu, Joshua LaBaer
We performed an unbiased proteome-scale profiling of humoral autoimmunity in recent-onset type 1 diabetes (T1D) patients and non-diabetic controls against ~10,000 human proteins using a Nucleic Acid Programmable Protein Array (NAPPA) platform, complemented by a knowledge-based selection of proteins from genes enriched in human pancreas. Although the global response was similar between cases and controls, we identified and then validated six specific novel T1D-associated autoantibodies (AAbs) with sensitivities that ranged from 16% to 27% at 95% specificity...
October 3, 2016: Journal of Proteome Research
Geert A Martens, Veerle De Punt, Geert Stangé
We quantified rat and human beta cell proteomes by LC-MS/MS searching for cell surface markers. In human beta cells, CD99 ranked among the plasma membrane proteins that associate a high molar abundance, to a relative degree of selectivity to the endocrine cells of the islets of Langerhans. Therefore, we investigated CD99's applicability as anchor for islet endocrine cell purification. We studied CD99 gene and protein expression by microarray, LC-MS/MS, Western blotting, flow cytometry and immunofluorescence and developed a protocol for magnetic bead-mediated beta cell enrichment from human pancreas digests using available anti-CD99 antibodies...
September 29, 2016: Journal of Tissue Engineering and Regenerative Medicine
Jong-Min Kim, Jun-Seop Shin, Byoung-Hoon Min, Hyun-Je Kim, Jung-Sik Kim, Il-Hee Yoon, Won-Young Jeong, Ga-Eul Lee, Min-Sun Kim, Ju-Eun Kim, Sang-Man Jin, Chung-Gyu Park
BACKGROUND: Diabetes mellitus (DM) model using streptozotocin (STZ) which induces chemical ablation of β cell in the pancreas has been widely used for various research purposes in non-human primates. However, STZ has been known to have a variety of adverse effects such as nephrotoxicity, hepatotoxicity, and even mortality. The purpose of this study is to report DM induction by STZ, toxicity associated with STZ and procedure and complication of exogenous insulin treatment for DM management in rhesus monkeys (Macaca mulatta) that are expected to be transplanted with porcine islets within 2 months...
September 27, 2016: Xenotransplantation
Rong Li, Jianhua Song, Wei Wu, Xinmou Wu, Min Su
In this study, we aim to explore the potential benefits of puerarin on metabolic function of liver fibrosis (LF) rat induced by carbon tetrachloride (CCl4), and to investigate with the underlying molecular mechanism targeted on liver and pancreas tissues. In methodology, The LF rats were prepared through intragastrically giving CCl4 twice each week (2ml/kg, v/w) for 8weeks, and dosed puerarin (20, 40mg/kg) were given three times each week via intraperitoneal injection. After being conducted with oral glucose tolerance test (OGTT), the blood samples of rat were harvested for biochemical tests, as well as the liver and pancreas were isolated for histological examination and biochemical assays...
September 24, 2016: Gene
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