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Pancreatic 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
Chen Luo, Lu-Ting Yu, Meng-Qi Yang, Xiang Li, Zhi-Yuan Zhang, Martin O Alfred, Jun-Li Liu, Min Wang
Regenerating genes (Reg) have been found during the search for factors involved in pancreatic islet regeneration. Our recent study discovered that pancreatic β-cell-specific overexpression of Reg3β protects against streptozotocin (Stz) -induced diabetes in mice. To investigate its potential roles in the treatment of diabetes, we produced a recombinant Reg3β protein and provided evidence that it is active in promoting islet β-cell survival against Stz- triggered cell death. Though ineffective in alleviating preexisting diabetes, pretreatment of recombinant Reg3β was capable of minimizing the Stz-induced hyperglycemia and weight loss, by preserving serum and pancreatic insulin levels, and islet β-cell mass...
October 21, 2016: Scientific Reports
Ingrid K Hals, Rinku Singh, Zuheng Ma, Hanne Scholz, Anneli Björklund, Valdemar Grill
We tested whether exposure of beta cells at reduced glucose leads to mitochondrial adaptions and whether such adaptions modulate effects of hypoxia. Rat islets, human islets and INS-1 832/13 cells were pre-cultured short term at half standard glucose concentrations (5.5 mM for rat islets and cells, 2.75 mM for human islets) without overtly negative effects on subsequently measured function (insulin secretion and cellular insulin contents) or on viability. Culture at half standard glucose upregulated complex I and tended to upregulate complex II in islets and INS-1 cells alike...
October 20, 2016: Islets
Chrysovalantou Mihailidou, Ioulia Chatzistamou, Athanasios G Papavassiliou, Hippokratis Kiaris
Pancreatic dysfunction during diabetes is linked to the induction of endoplasmic reticulum (ER) stress on pancreatic beta (β) cells. Our laboratory recently discovered that p21 protects from diabetes by modifying the outcome of ER stress response. In the present study, we explored the antidiabetic activity of ciclopirox (CPX), an iron chelator and recently described activator of p21 expression. The effects of CPX in beta cell survival and function were assessed in cultured islets in vitro as well as in diabetic mice in vivo...
October 19, 2016: Pflügers Archiv: European Journal of Physiology
Saeide-Sadat Shobeiri, Saeid Abediankenari, Bahareh Lashtoo-Aghaee, Zahra Rahmani, Bahareh Esmaeili-Gorji
BACKGROUND: Research says that diabetes may develop in over 10% of non-diabetic pregnant women. Diabetes which generally occurs late in second trimester and third trimester of pregnancy, it is called gestational diabetes. Overweight or suffering from obesity before pregnancy is type 2 diabetes risk factor. In most cases, diabetic symptoms disappear after delivery. HLA-G has an important role both in mother and fetus tolerance during pregnancy, it may also be effective in the protection of pancreatic islet cells...
2016: Caspian Journal of Internal Medicine
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
Li Ding, Yue Yin, Lingling Han, Yin Li, Jing Zhao, Weizhen Zhang
Neurogenin3-driven deletion of tuberous sclerosis complex 1 (Tsc1) activated mechanistic target of rapamycin complex 1 (mTORC1) measured by up-regulation of mTOR and S6 phosphorylation in islet cells. Neurogenin3-Tsc1-/- mice demonstrated a significant increase in average islet size and mean area of individual islet cell. Insulin mRNA and plasma insulin levels increased significantly after weaning. Glucagon mRNA and plasma levels increased in neonate followed by modest reduction in adult. Somatostatin mRNA and plasma levels markedly increased...
October 17, 2016: Journal of Endocrinology
Yutong Su, Xiuli Jiang, Yanli Li, Feng Li, Yulong Cheng, Ying Peng, Dalong Song, Jie Hong, Guang Ning, Yanan Cao, Weiqing Wang
The mechanism underlying the increased susceptibility of type 2 diabetes in offspring of maternal malnutrition is poorly determined. Here we tested the hypothesis that functional microRNAs (miRNAs) mediated the maternal low protein (LP) isocaloric diet induced pancreatic β-cell impairment. We performed miRNA profiling in the islets from offspring of LP and control diet mothers to explore the potential functional miRNAs responsible for β-cell dysfunction. We found that LP offspring exhibited impaired glucose tolerance due to decreased β-cell mass and insulin secretion...
October 18, 2016: Endocrinology
Kristen E Syring, Kayla A Boortz, James K Oeser, Alessandro Ustione, Kenneth A Platt, Melanie K Shadoan, Owen P McGuinness, David W Piston, David R Powell, Richard M O'Brien
Polymorphisms in the SLC30A8 gene, which encodes the ZnT8 zinc transporter, are associated with altered susceptibility to type 2 diabetes (T2D) and SLC30A8 haploinsufficiency is protective against the development of T2D in obese humans. SLC30A8 is predominantly expressed in pancreatic islet beta cells but surprisingly multiple knockout mouse studies have shown little effect of Slc30a8 deletion on glucose tolerance or glucose-stimulated insulin secretion (GSIS). Multiple other Slc30a isoforms are expressed at low levels in pancreatic islets...
October 18, 2016: Endocrinology
Jing-Woei Li, Heung-Man Lee, Ying Wang, Amy Hin-Yan Tong, Kevin Y Yip, Stephen Kwok-Wing Tsui, Si Lok, Risa Ozaki, Andrea O Luk, Alice P S Kong, Wing-Yee So, Ronald C W Ma, Juliana C N Chan, Ting-Fung Chan
Protein interactions play significant roles in complex diseases. We analyzed peripheral blood mononuclear cells (PBMC) transcriptome using a multi-method strategy. We constructed a tissue-specific interactome (T2Di) and identified 420 molecular signatures associated with T2D-related comorbidity and symptoms, mainly implicated in inflammation, adipogenesis, protein phosphorylation and hormonal secretion. Apart from explaining the residual associations within the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) study, the T2Di signatures were enriched in pathogenic cell type-specific regulatory elements related to fetal development, immunity and expression quantitative trait loci (eQTL)...
October 18, 2016: Scientific Reports
Chafiq Hamdouchi, Steven D Kahl, Anjana Patel Lewis, Guemalli R Cardona, Richard W Zink, Keyue Chen, Thomas E Eessalu, James V Ficorilli, Marialuisa C Marcelo, Keith A Otto, Kelly L Wilbur, Jayana P Lineswala, Jared L Piper, D Scott Coffey, Stephanie A Sweetana, Joseph V Haas, Dawn A Brooks, Edward J Pratt, Ruth M Belin, Mark A Deeg, Xiaosu Ma, Ellen A Cannady, Jason T Johnson, Nathan P Yumibe, Qi Chen, Pranab Maiti, Chahrzad Montrose-Rafizadeh, Yanyun Chen, Anne Reifel Miller
The G protein-coupled receptor 40 (GPR40) also known as Free Fatty Acid Receptor 1 (FFAR1) is highly expressed in pancreatic, islet cells and responds to endogenous fatty acids resulting in amplification of insulin secretion only in the presence of elevated glucose levels. Hypothesis driven structural modifications to endogenous FFAs, focused on breaking planarity and reducing lipophilicity, led to the identification of spiropiperidine and tetrahydroquinoline acid derivatives as GPR40 agonists with unique pharmacology, selectivity and pharmacokinetic properties...
October 17, 2016: Journal of Medicinal Chemistry
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
Roi Isaac, Ido Goldstein, Noa Furth, Neta Zilber, Sarina Streim, Sigalit Boura-Halfon, Eytan Elhanany, Varda Rotter, Moshe Oren, Yehiel Zick
Earlier reported small interfering RNA (siRNA) high-throughput screens, identified seven-transmembrane superfamily member 3 (TM7SF3) as a novel inhibitor of pancreatic β-cell death. Here we show that TM7SF3 maintains protein homeostasis and promotes cell survival through attenuation of ER stress. Overexpression of TM7SF3 inhibits caspase 3/7 activation. In contrast, siRNA-mediated silencing of TM7SF3 accelerates ER stress and activation of the unfolded protein response (UPR). This involves inhibitory phosphorylation of eukaryotic translation initiation factor 2α activity and increased expression of activating transcription factor-3 (ATF3), ATF4 and C/EBP homologous protein, followed by induction of apoptosis...
October 14, 2016: Cell Death and Differentiation
J Ciriza, L Saenz Del Burgo, R M Hernández, G Orive, J L Pedraz
Alginate cell microencapsulation implies the immobilization of cells within a polymeric membrane that allows the bidirectional diffusion of nutrients and oxygen inside the microcapsules and the release of waste and therapeutic molecules outside them. This technology has been applied to several cell types and it has been extensively described with pancreatic islets. However, other cells such as myoblasts are being currently studied and showing high interest. Moreover, different systems and approaches have been developed for cell encapsulation such as electrostatic extrusion and Flow focusing technology...
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
John Patrick McQuilling, Emmanuel C Opara
A major obstacle to long-term performance of tissue construct implants in regenerative medicine is the inherent hypoxia to which cells in the engineered construct are exposed prior to vascularization of the implant. Various approaches are currently being designed to address this problem. An emerging area of interest on this issue is the use of peroxide-based materials to generate oxygen during the critical period of extended hypoxia that occurs from the time cells are in culture waiting to be used in tissue engineering devices through the immediate post-implant period...
2017: Methods in Molecular Biology
Marcus D Darabbie, Emmanuel C Opara
The promise of pancreatic islet transplantation is hindered by organ shortage, and the need for immunosuppression of transplant recipient in order to prevent rejection. Alginate microencapsulation can overcome these hurdles; however further optimization of this technique is required. Among the critical factors to be optimized is the durability of alginate microcapsules, which can be determined by their mechanical strength tests. Here we describe several simple and reliable methods to assist in assessing the mechanical strength of alginate beads...
2017: Methods in Molecular Biology
William F Kendall, Emmanuel C Opara
Application of microencapsulation to the immunoisolation of pancreatic islets holds promise for expanding the use of islet transplantation as a treatment option for Type 1 diabetes. It is generally believed that successful development of a reliable methodology will ideally allow for transplantation of pancreatic islets that are protected from the immune system, thereby obviating the need for the use of immunosuppressive drugs and their attendant side effects. In addition, this technology has the potential to expand the donor pool as islets from nonhuman donors could be used as xenografts in human patients...
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
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