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Islet cells

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
Bradley P Weegman, Ahmad Essawy, Peter Nash, Alexandra L Carlson, Kristin J Voltzke, Zhaohui Geng, Marjan Jahani, Benjamin B Becker, Klearchos K Papas, Meri T Firpo
In this demonstration, spheroids formed from the β-TC6 insulinoma cell line were cultured as a model of manufacturing a mammalian islet cell product to demonstrate how regulating nutrient levels can improve cell yields. In previous studies, bioreactors facilitated increased culture volumes over static cultures, but no increase in cell yields were observed. Limitations in key nutrients such as glucose, which were consumed between batch feedings, can lead to limitations in cell expansion. Large fluctuations in glucose levels were observed, despite the increase in glucose concentrations in the media...
September 25, 2016: Journal of Visualized Experiments: JoVE
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
Kevin Vivot, Malika A Benahmed, Elodie Seyfritz, William Bietiger, Karim Elbayed, Elisa Ruhland, Allan Langlois, Elisa Maillard, Michel Pinget, Nathalie Jeandidier, Jean-Pierre Gies, Izzie-Jacques Namer, Séverine Sigrist, Nathalie Reix
Intrahepatic transplantation of islets requires a lot of islets because more than 50% of the graft is lost during the 24 hours following transplantation. We analyzed, in a rat model, early post-transplantation inflammation using systemic inflammatory markers, or directly in islet-transplanted livers by immunohistochemistry. (1)H HRMAS NMR was employed to investigate metabolic responses associated with the transplantation. Inflammatory markers (Interleukin-6, α2-macroglobulin) are not suitable to follow islet reactions as they are not islet specific...
2016: International Journal of Biological Sciences
Tina M Mitre, Anmar Khadra, Massimo Pietropaolo
The expression level of tissue-restricted autoantigens (TSA) in the thymus is crucial for the negative selection of autoreactive T cells during central tolerance. The autoimmune regulator factor (AIRE) plays an important role in the positive regulation of these TSA in medullary thymic epithelial cells and, consequently, in the negative selection of high-avidity autoreactive T cells. Recent studies, however, revealed that thymic islet cell autoantigen (ICA69) expression level in non-obese diabetic (NOD) mice, prone to developing type 1 diabetes (T1D), is reduced due to an increase in the binding affinity of AIRE to the Ica1-promoter region, which regulates ICA69 protein synthesis...
October 17, 2016: Mathematical Biosciences
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
Attilio Pingitore, Edward S Chambers, Thomas Hill, Inmaculada Ruz Maldonado, Bo Liu, Gavin Bewick, Douglas J Morrison, Tom Preston, Gareth A Wallis, Catriona Tedford, Ramón Castañera González, Guo Cai Huang, Pratik Choudhary, Gary Frost, Shanta J Persaud
AIMS: Diet-derived short chain fatty acids (SCFAs) improve glucose homeostasis in vivo, but the role of individual SCFAs and their mechanisms of action have not been defined. This study evaluated the effects of increasing colonic delivery of the SCFA propionate on β-cell function in humans and the direct effects of propionate on isolated human islets in vitro. MATERIALS AND METHODS: For 24 weeks human subjects ingested an inulin-propionate ester that delivers propionate to the colon...
October 20, 2016: Diabetes, Obesity & Metabolism
Yoichi Oikawa, Hajime Tanaka, Junko Uchida, Yoshihiro Atsumi, Masaya Osawa, Takeshi Katsuki, Toshihide Kawai, Akira Shimada
Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM), believed to be caused by β-cell destruction through islet-cell autoimmunity, gradually progresses to an insulin-dependent state over time. Although the presence of anti-glutamic acid decarboxylase antibody (GADA) is required for the diagnosis of SPIDDM, a recent change in the GADA assay kit from radioimmunoassay (RIA) to enzyme-linked immunosorbent assay (ELISA) yields mismatched GADA test results between the two kits, leading to confusion in understanding the pathological conditions of SPIDDM in Japan...
October 18, 2016: Endocrine Journal
Q F Liang, C Gao, H Liang, B Li, X H Du, Antoine Labbe
Objective: To observe the characteristics of pterygium with in vivo confocal microscopy (IVCM) and understand pterygium activity with the density of inflammatory cells, formation of new blood vessels, and the number of activated keratocytes within the stroma. Methods: A prospective case-controlled study. Thirty-six pterygia from 28 patients were analyzed in this study. A pterygium activity score was obtained by summing four scores of ocular discomfort, pterygium hyperemia, keratitis, and the presence of Fuchs patches...
October 11, 2016: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
Ying Wei, Jun Lu, Tong Lu, Feihong Meng, Jia Xu, Li Wang, Yang Li, Liping Wang, Fei Li
Prefibrillar amyloid aggregates of proteins are known as cytotoxic species and a common pathogenic factor for many degenerative diseases. The mechanism underlying the formation and cytotoxicity of prefibrillar aggregates is believed to be independent of the actual nature of the amyloid protein. In this study, we monitored the formation of the peptide oligomers and examined the disruptive effects of the oligomers on liposomes using the human islet amyloid polypeptide fragment hIAPP18-27 as a model peptide. We observed various morphologies of oligomers formed at different aggregation stages that precede the formation of mature amyloid fibrils...
October 19, 2016: Physical Chemistry Chemical Physics: PCCP
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
Jie Qin, Yusuke Arakawa, Miwa Morita, John J Fung, Shiguang Qian, Lina Lu
BACKGROUND: Islet transplantation is a promising therapeutic approach for restore the physical response to blood glucose in type 1 diabetes. Current chronic use of immunosuppressive reagents for preventing islet allograft rejection is associated with severe complications. In addition, many of the immunosuppressive drugs are diabetogenic. The induction of transplant tolerance to eliminate the dependency on immunosuppression is ideal, but remains challenging. METHODS: Addition of hepatic stellate cells allowed generation of myeloid-derived suppressor cells (MDSC) from precursors in mouse bone marrow...
October 17, 2016: Transplantation
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
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
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
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