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Endocrine pancreas

Igor Arregi, Maria Climent, Dobromir Iliev, Jürgen Strasser, Nadège Gouignard, Jenny K Johansson, Tania Singh, Magdalena Mazur, Henrik Semb, Isabella Artner, Liliana Minichiello, Edgar M Pera
Vitamin A-derived retinoic acid (RA) signals are critical for the development of several organs, including the pancreas. However, the tissue-specific control of RA synthesis in organ and cell lineage development has only poorly been addressed in vivo. Here we show that Retinol dehydrogenase-10 (Rdh10), a key enzyme in embryonic RA production, has important functions in pancreas organogenesis and endocrine cell differentiation. Rdh10 was expressed in the developing pancreas epithelium and surrounding mesenchyme...
October 14, 2016: Endocrinology
Karolína Drbalová, Kateřina Herdová, Petr Krejčí, Monika Nývltová, Svatopluk Solař, Lenka Vedralová, Pavel Záruba, David Netuka, Petr Bavor
Multiple Endocrine Neoplasia (MEN) is a condition in which several endocrine organs of an individual are affected by adenoma, hyperplasia and less often carcinoma, either simultaneously or at different stages of life. Two existing syndromes, MEN1 and MEN2 (2A, 2B), in literature is also mentioned MEN4, are associated also with other non-endocrine disorders. MEN1 (Wermer syndrome) affects the pituitary, parathyroid, and pancreatic area. 95 % of patients show very early manifestation of hyperparathyroidism, often before 40 years of age...
2016: Vnitr̆ní Lékar̆ství
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
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
Masataka Kunii, Mica Ohara-Imaizumi, Noriko Takahashi, Masaki Kobayashi, Ryosuke Kawakami, Yasumitsu Kondoh, Takeshi Shimizu, Siro Simizu, Bangzhong Lin, Kazuto Nunomura, Kyota Aoyagi, Mitsuyo Ohno, Masaki Ohmuraya, Takashi Sato, Shin-Ichiro Yoshimura, Ken Sato, Reiko Harada, Yoon-Jeong Kim, Hiroyuki Osada, Tomomi Nemoto, Haruo Kasai, Tadahiro Kitamura, Shinya Nagamatsu, Akihiro Harada
The membrane fusion of secretory granules with plasma membranes is crucial for the exocytosis of hormones and enzymes. Secretion disorders can cause various diseases such as diabetes or pancreatitis. Synaptosomal-associated protein 23 (SNAP23), a soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor (SNARE) molecule, is essential for secretory granule fusion in several cell lines. However, the in vivo functions of SNAP23 in endocrine and exocrine tissues remain unclear. In this study, we show opposing roles for SNAP23 in secretion in pancreatic exocrine and endocrine cells...
October 10, 2016: Journal of Cell Biology
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
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
Maayan Baron, Adrian Veres, Samuel L Wolock, Aubrey L Faust, Renaud Gaujoux, Amedeo Vetere, Jennifer Hyoje Ryu, Bridget K Wagner, Shai S Shen-Orr, Allon M Klein, Douglas A Melton, Itai Yanai
Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual pancreatic cells from four human donors and two mouse strains. Cells could be divided into 15 clusters that matched previously characterized cell types: all endocrine cell types, including rare epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and activated stellate cells; and four types of immune cells...
September 21, 2016: Cell Systems
Rudi Tong, Rebecca C Wade, Neil J Bruce
The enzyme adenylyl cyclase (AC) plays a pivotal role in a variety of signal transduction pathways inside the cell, where it catalyzes the cyclization of adenosine triphosphate (ATP) into the second- messenger cyclic adenosine monophosphate (cAMP). Among other roles, AC regulates processes involved in neural plasticity, innervation of smooth muscles of the heart and the endocrine system of the pancreas. The functional diversity of AC is manifested in its different isoforms, each having a specific regulation pattern...
September 26, 2016: Proteins
Michael J Shamblott, Marci L O'Driscoll, Danielle L Gomez, Dustin L McGuire
BACKGROUND: Reports of exocrine-to-endocrine reprogramming through expression or stabilization of the transcription factor neurogenin 3 (NGN3) have generated renewed interest in harnessing pancreatic plasticity for therapeutic applications. NGN3 is expressed by a population of endocrine progenitor cells that give rise exclusively to hormone-secreting cells within pancreatic islets and is necessary and sufficient for endocrine differentiation during development. In the adult human pancreas, NGN3 is expressed by dedifferentiating exocrine cells with a phenotype resembling endocrine progenitor cells and the capacity for endocrine differentiation in vitro...
2016: Cell Communication and Signaling: CCS
Ananta Poudel, Jonas L Fowler, Mark C Zielinski, German Kilimnik, Manami Hara
The large size of human tissues requires a practical stereological approach to perform a comprehensive analysis of the whole organ. We have developed a method to quantitatively analyze the whole human pancreas, as one of the challenging organs to study, in which endocrine cells form various sizes of islets that are scattered unevenly throughout the exocrine pancreas. Furthermore, the human pancreas possesses intrinsic characteristics of intra-individual variability, i.e. regional differences in endocrine cell/islet distribution, and marked inter-individual heterogeneity regardless of age, sex and disease conditions including obesity and diabetes...
2016: Scientific Reports
Song Lee, Seonghee Jeong, Chanmi Lee, Jooyun Oh, Song-Cheol Kim
Mesenchymal stem cells (MSCs) derived from bone marrow, adipose tissue, and most connective tissues have been recognized as promising sources for cell-based therapies. MSCs have also been detected in human pancreatic tissue, including endocrine and exocrine cells. These adult human pancreas-derived MSCs have generated a great deal of interest owing to their potential use in the differentiation of insulin-producing cells for diabetes treatment. In the present study, we isolated MSCs from the adult human exocrine pancreas to determine whether isolated MSCs have the potential to differentiate into pancreatic endocrine cells and, therefore, whether they can be used in stem cell-based therapies...
2016: Stem Cells International
Stephan Kruger, Michael Haas, Philipp Johannes Burger, Steffen Ormanns, Dominik Paul Modest, Christoph Benedikt Westphalen, Axel Kleespies, Martin Kurt Angele, Werner Hartwig, Christiane Josephine Bruns, Thomas Kirchner, Jens Werner, Volker Heinemann, Stefan Boeck
PURPOSE: Acinar cell carcinoma (ACC) of the pancreas is a very rare cancer, constituting 1 % of all malignant non-endocrine pancreatic tumors. Only very limited data exist to guide treatment in patients with advanced ACC. METHODS: Between 2000 and 2015, 15 patients with ACC were diagnosed and/or treated at our high-volume comprehensive cancer center. Medical records and correlating serum levels of the potential serum tumor markers CA 19-9, CEA and lipase were analyzed retrospectively...
September 14, 2016: Journal of Cancer Research and Clinical Oncology
Sayuan Liang, Karim Louchami, Hauke Kolster, Anna Jacobsen, Ying Zhang, Julian Thimm, Abdullah Sener, Joachim Thiem, Willy Malaisse, Tom Dresselaers, Uwe Himmelreich
The assessment of the β-cell mass in experimental models of diabetes and ultimately in patients is a hallmark to understand the relationship between reduced β-cell mass/function and the onset of diabetes. It has been shown before that the GLUT-2 transporter is highly expressed in both β-cells and hepatocytes and that D-mannoheptulose (DMH) has high uptake specificity for the GLUT-2 transporter. As 19-fluorine MRI has emerged as a new alternative method for MRI cell tracking because it provides potential non-invasive localization and quantification of labeled cells, the purpose of this project is to validate β-cell and pancreatic islet imaging by using fluorinated, GLUT-2 targeting mannoheptulose derivatives ((19) FMH) both in vivo and ex vivo...
September 14, 2016: Contrast Media & Molecular Imaging
Nobuo Ashizawa, Toshio Sakai, Tsunao Yoneyama, Yoshikazu Kinoshita
No abstract text is available yet for this article.
October 2016: Pancreas
Marta García-Arévalo, Paloma Alonso-Magdalena, Joan-Marc Servitja, Talía Boronat, Beatriz Merin, Sabrina Villar, Gema Medina-Gómez, Anna Novials, Ivan Quesada, Angel Nadal
Alterations during development of metabolic key organs such as the endocrine pancreas affect the phenotype later in life. There is evidence that in utero or perinatal exposure to bisphenol-A (BPA), leads to impaired glucose metabolism during adulthood. However, how BPA exposure during pregnancy affects pancreatic β-cell growth and function in offspring during early life has not been explored. We exposed pregnant mice to either vehicle (Control) or BPA (10 and 100 μ g/kg/day, BPA10 and BPA100) and examined offspring on postnatal days (P) P0, P21, P30 and P120...
September 13, 2016: Endocrinology
Lina Zhang, Giacomo Lanzoni, Matteo Battarra, Luca Inverardi, Qibin Zhang
: The etiology of Type 1 Diabetes (T1D) remains elusive. Enzymatically isolated and cultured (EIC) islets cannot fully reflect the natural protein composition and disease process of in vivo islets, because of the stress from isolation procedures. In order to study islet protein composition in conditions close to the natural environment, we performed proteomic analysis of EIC islets, and laser capture microdissected (LCM) human islets and acinar tissue from fresh-frozen pancreas sections of three cadaveric donors...
September 13, 2016: Journal of Proteomics
V Cigliola, F Thorel, S Chera, P L Herrera
The different forms of diabetes mellitus differ in their pathogenesis but, ultimately, they are all characterized by progressive islet β-cell loss. Restoring the β-cell mass is therefore a major goal for future therapeutic approaches. The number of β-cells found at birth is determined by proliferation and differentiation of pancreatic progenitor cells, and it has been considered to remain mostly unchanged throughout adult life. Recent studies in mice have revealed an unexpected plasticity in islet endocrine cells in response to stress; under certain conditions, islet non-β-cells have the potential to reprogram into insulin producers, thus contributing to restore the β-cell mass...
September 2016: Diabetes, Obesity & Metabolism
C Honoré, C Rescan, J Hald, P S McGrath, M B K Petersen, M Hansson, T Klein, S Østergaard, J M Wells, O D Madsen
During embryonic development, endocrine cells of the pancreas are specified from multipotent progenitors. The transcription factor Neurogenin 3 (NEUROG3) is critical for this development and it has been shown that all endocrine cells of the pancreas arise from endocrine progenitors expressing NEUROG3. A thorough understanding of the role of NEUROG3 during development, directed differentiation of pluripotent stem cells and in models of cellular reprogramming, will guide future efforts directed at finding novel sources of β-cells for cell replacement therapies...
September 2016: Diabetes, Obesity & Metabolism
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