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Ins 1e

Maciej Sassek, Ewa Pruszynska-Oszmalek, Paweł A Kołodziejski, Dawid Szczepankiewicz, Przemyslaw Kaczmarek, Marianna Wieloch, Katarzyna Kurto, Leszek Nogowski, Krzysztof W Nowak, Mathias Z Strowski, Pawel Mackowiak
Resistin participates in the regulation of energy homeostasis, insulin resistance, and inflammation. The potential expression in pancreas, and modulation of the endocrine pancreas secretion by resistin is not well characterized, therefore, we examined it on several levels. We examined the localization of resistin in rat pancreatic islets by immunohistochemistry and immunofluorescence, and the potential presence of resistin mRNA by RT-PCR and protein by Western Blot in these structures. In addition, we studied the regulation of insulin and glucagon secretion by resistin in pancreatic INS-1E β- and InR-G9 α-cell lines as well as isolated rat pancreatic islets...
October 31, 2016: Islets
Michela Novelli, Marta Menegazzi, Pascale Beffy, Svetlana Porozov, Alex Gregorelli, Daniela Giacopelli, Vincenzo De Tata, Pellegrino Masiello
The extract of the herbaceous plant St. John's wort (SJW) and its phloroglucinol component hyperforin (HPF) were previously shown to inhibit cytokine-induced STAT-1 and NF-κB activation and prevent damage in pancreatic β cells. To further clarify the mechanisms underlying their protective effects, we evaluated the phosphorylation state of various factors of cytokine signaling pathways and the expression of target genes involved in β-cell function, inflammatory response and apoptosis induction. In the INS-1E β-cell line, exposed to a cytokine mixture with/without SJW extract (2-5μg/ml) or HPF (1-5μM), protein phosphorylation was assessed by western blotting and expression of target genes by real-time quantitative PCR...
October 22, 2016: International Journal of Biochemistry & Cell Biology
Ranhua Xiong, Freya Joris, Sayuan Liang, Riet De Rycke, Saskia Lippens, Jo Demeester, Andre Skirtach, Koen Raemdonck, Uwe Himmelreich, Stefaan C De Smedt, Kevin Braeckmans
Long-term in vivo imaging of cells is crucial for the understanding of cellular fate in biological processes in cancer research, immunology, or in cell-based therapies such as beta cell transplantation in type I diabetes or stem cell therapy. Traditionally, cell labeling with the desired contrast agent occurs ex vivo via spontaneous endocytosis, which is a variable and slow process that requires optimization for each particular label-cell type combination. Following endocytic uptake, the contrast agents mostly remain entrapped in the endolysosomal compartment, which leads to signal instability, cytotoxicity, and asymmetric inheritance of the labels upon cell division...
October 3, 2016: Nano Letters
Kaidu H Barrosa, Murilo C Mecchi, Daniela G Rando, Ari José S Ferreira, Patricia Sartorelli, Maíra M R Valle, Silvana Bordin, Luciana C Caperuto, João Henrique G Lago, Camilo Lellis-Santos
Despite its common use, the synthetic glucocorticoid dexamethasone can cause several adverse effects, such as diabetes and insulin-related metabolic impairment. Thus, research on molecules that could provide the same anti-inflammatory response with milder side effects is constant. In this work the anti-inflammatory activity of the natural sesquiterpene polygodial, extracted from the endemic Brazilian plant Drimys brasiliensis Miers (Winteraceae), was investigated. Employing a pancreatic β-cell model (INS 1E), the effect of polygodial on signaling pathways is similar to that caused by dexamethasone - both increased MKP1 and decreased ERK1/2 expression in a dose-response and time-dependent manner...
October 25, 2016: Chemico-biological Interactions
Nunzia Caporarello, Mario Salmeri, Marina Scalia, Carla Motta, Cristina Parrino, Lucia Frittitta, Melania Olivieri, Martina Cristaldi, Roberto Avola, Vincenzo Bramanti, Maria Antonietta Toscano, Carmelina Daniela Anfuso, Gabriella Lupo
It is suspected that microbial infections take part in the pathogenesis of diabetes mellitus type 1 (T1DM). Glucose-induced insulin secretion is accompanied by the release of free arachidonic acid (AA) mainly by cytosolic- and calcium independent phospholipases A2 (cPLA2 and iPLA2). Insulinoma cell line (INS-1E) was infected with E. coli isolated from the blood culture of a patient with sepsis. Invasion assay, Scanning Electron Microscopy and Transmission Electron Microscopy demonstrated the capacity of E. coli to enter cells, which was reduced by PLA2 inhibitors...
2016: PloS One
Bijun Zhang, Guangrui Lai, Jingjing Wu, Ru Sun, Runhong Xu, Xianghong Yang, Yafei Qi, Yanyan Zhao
We previously generated cytochrome P450 4F2 (CYP4F2) transgenic mice that have high levels of 20-hydroxyeicosatetraenoic acid (20-HETE) production; these mice exhibit both hypertension and hyperglycemia without insulin resistance. Currently, it is unclear whether and how 20-HETE affects insulin secretion, thus resulting in hyperglycemia. In this study, we found that 20-HETE attenuated glucose-stimulated insulin secretion (GSIS) in CYP4F2 transgenic mice as well as in rat insulinoma INS-1E cells treated with 0...
August 27, 2016: Endocrine
Tuyet Thi Nguyen, Xianglan Quan, Shanhua Xu, Ranjan Das, Seung-Kuy Cha, In Deok Kong, Minho Shong, Claes B Wollheim, Kyu-Sang Park
Elevated plasma levels of inorganic phosphate (Pi) are harmful, causing, among other complications, vascular calcification and defective insulin secretion. The underlying molecular mechanisms of these complications remain poorly understood. We demonstrated the role of Pi transport across the plasmalemma on Pi toxicity in INS-1E rat clonal β cells and rat pancreatic islet cells. Type III sodium-phosphate cotransporters (NaPis) are the predominant Pi transporters expressed in insulin-secreting cells. Transcript and protein levels of sodium-dependent phosphate transporter 1 and 2 (PiT-1 and -2), isotypes of type III NaPi, were up-regulated by high-Pi incubation...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Zhenping Liu, Per B Jeppesen, Søren Gregersen, Lotte Bach Larsen, Kjeld Hermansen
BACKGROUND: Pancreatic islet-cell dysfunction is a hallmark in the development of diabetes, but the reasons for the primary β-cell defect are still elusive. Elevated circulating proline levels have been found in subjects with insulin resistance, obesity, and type 2 diabetes. Therefore, we assessed β-cell function, gene expressions, and cell death after long-term exposure of pancreatic β-cells to excess proline in vitro. METHODS: Isolated mouse islets and INS-1E cells were incubated with and without excess proline...
2016: Review of Diabetic Studies: RDS
Søren Fisker Schmidt, Jesper Grud Skat Madsen, Kari Østerli Frafjord, Lars la Cour Poulsen, Sofia Salö, Michael Boergesen, Anne Loft, Bjørk Ditlev Larsen, Maria Stahl Madsen, Jens Juul Holst, Pierre Maechler, Louise Torp Dalgaard, Susanne Mandrup
Glucose is an important inducer of insulin secretion, but it also stimulates long-term adaptive changes in gene expression that can either promote or antagonize the proliferative potential and function of β cells. Here, we have generated time-resolved profiles of enhancer and transcriptional activity in response to glucose in the INS-1E pancreatic β cell line. Our data outline a biphasic response with a first transcriptional wave during which metabolic genes are activated, and a second wave where cell-cycle genes are activated and β cell identity genes are repressed...
August 30, 2016: Cell Reports
Zhijie Chen, Hui-Wang Ai
Genetically encoded fluorescent Zn(2+) indicators (GEZIs) are highly attractive research tools for studying Zn(2+) homeostasis and signaling in mammalian cells. Most current GEZIs are based on Förster resonance energy transfer (FRET) between a select pair of fluorescent proteins (FPs) fused with Zn(2+)-binding motifs. One drawback of such FRET-based GEZIs is their broad spectral profile bandwidths, creating challenges when monitoring multiple targets or parameters. To address this issue, we have engineered a group of intensiometric GEZIs based on single teal and red FPs that can be utilized to monitor subcellular Zn(2+) diffusion and glucose-induced Zn(2+) secretion in pancreatic INS-1E β-cells...
September 20, 2016: Analytical Chemistry
Han Sung Kim, Yeong-Min Yoo
Autophagy appears to be involved in maintaining normal intracellular insulin content by accelerating the insulin degradation rate in β-cells (Marsh et al., 2007) [1]. 2-deoxy-d-glucose (2-DG) is metabolized by hexokinase, and acts as an inhibitor of glycolysis. 2-DG triggers glucose deprivation without altering other nutrients or metabolic pathways (Aghaee et al., 2012) [2], and appears to be an ideal tool for studying autophagy. Rapamycin induced upregulation of autophagy in both cultured isolated islets and pancreatic β-cells (Tanemura et al...
September 2016: Data in Brief
Han Sung Kim, Tae-Young Han, Yeong-Min Yoo
2-DG triggers glucose deprivation without altering other nutrients or metabolic pathways and then activates autophagy via activation of AMPK and endoplasmic reticulum (ER) stress. We investigated whether 2-DG reduced intracellular insulin increased by melatonin via autophagy/EDC3 in insulinoma INS-1E cells. p-AMPK and GRP78/BiP level were significantly increased by 2-DG in the presence/absence of melatonin, but IRE1α level was reduced in 2-DG treatment. Levels of p85α, p110, p-Akt (Ser473, Thr308), and p-mTOR (Ser2481) were also significantly reduced by 2-DG in the presence/absence of melatonin...
2016: Oxidative Medicine and Cellular Longevity
M F Graciano, M Leonelli, R Curi, A R Carpinelli
Omega-3 fatty acids have multiple effects in peripheral tissues and pancreatic beta cell function. Dietary depletion of omega-3 fatty acids is associated with pancreatic islet dysfunction and insulin resistance in rats. Herein, the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on pancreatic beta cell redox state and function were investigated. INS-1E insulin-secreting cells were incubated with EPA and DHA in combination with palmitic acid, and productions of reactive oxygen species (ROS), nitric oxide (NO) and insulin were measured...
December 2016: Journal of Physiology and Biochemistry
Zahra Azizi, Claudia Lange, Federico Paroni, Amin Ardestani, Anke Meyer, Yonghua Wu, Axel R Zander, Christof Westenfelder, Kathrin Maedler
Bone marrow mesenchymal stromal cells (MSC) have anti-inflammatory, anti-apoptotic and immunosuppressive properties and are a potent source for cell therapy. Cell fusion has been proposed for rapid generation of functional new reprogrammed cells. In this study, we aimed to establish a fusion protocol of bone marrow-derived human MSCs with the rat beta-cell line (INS-1E) as well as human isolated pancreatic islets in order to generate insulin producing beta-MSCs as a cell-based treatment for diabetes.Human eGFP+ puromycin+ MSCs were co-cultured with either stably mCherry-expressing rat INS-1E cells or human dispersed islet cells and treated with phytohemagglutinin (PHA-P) and polyethylene glycol (PEG) to induce fusion...
June 21, 2016: Oncotarget
Ana Cláudia Munhoz, Patrícia Riva, Daniel Simões, Rui Curi, Angelo Rafael Carpinelli
Mitochondria and NADPH oxidase are important sources of reactive oxygen species in particular the superoxide radical (ROS) in pancreatic islets. These molecules derived from molecular oxygen are involved in pancreatic β-cells signaling and control of insulin secretion. We examined the involvement of ROS produced through NADPH oxidase in the leucine- and/or glucose-induced insulin secretion by pancreatic islets from fed or 48-hour fasted rats. Glucose-stimulated insulin secretion (GSIS) in isolated islets was evaluated at low (2...
2016: PloS One
Eddy Himpe, Daniel A Cunha, Imane Song, Marco Bugliani, Piero Marchetti, Miriam Cnop, Luc Bouwens
OBJECTIVE: Previous studies demonstrated that a phenylpropenoic acid glucoside (PPAG) from rooibos (Aspalathus linearis) extract had anti-hyperglycemic activity and significant protective effects on the pancreatic beta cell mass in a chronic diet-induced diabetes model. The present study evaluated the cytoprotective effect of the phytochemical on beta cells exposed to acute cell stress. METHODS: Synthetically prepared PPAG was administered orally in mice treated with a single dose of streptozotocin to acutely induce beta cell death and hyperglycemia...
2016: PloS One
Svetlana N Rylova, Beatrice Waser, Luigi Del Pozzo, Roswitha Tönnesmann, Rosalba Mansi, Philipp T Meyer, Jean Claude Reubi, Helmut R Maecke
UNLABELLED: The glucagon-like peptide-1 (GLP-1) receptors are important biomarkers for imaging pancreatic β-cell mass and detection of benign insulinomas. Using GLP-1 receptor antagonists, we aimed to eliminate the insulin-related side effects reported for all GLP-1 receptor agonists. Additionally, using a nonresidualizing tracer, (125)I-Bolton-Hunter-Exendin(9-39)NH2 ((125)I-BH-Ex(9-39)NH2), we aimed to reduce the high kidney uptake, enabling a better detection of insulinomas in the tail and head of the pancreas...
August 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
A Raiter, A Tenenbaum, M Yackobovitch-Gavan, A Battler, B Hardy
BACKGROUND AND OBJECTIVES: Diabetes Type 1 is characterized by hyperglycemia due to reduced insulin secretion that results from the death of pancreatic β cells. It was suggested that endoplasmic reticulum (ER) stress is associated with the autoimmune-mediated β cell destruction. Glucose regulated protein 78 (GRP78) functions as a key regulator to maintain the ER function. Under stress conditions GRP78 is up-regulated and expressed on the cell surface serving as a signaling receptor...
April 2016: Experimental and Clinical Endocrinology & Diabetes
Annalisa Natalicchio, Giuseppina Biondi, Nicola Marrano, Rossella Labarbuta, Federica Tortosa, Rosaria Spagnuolo, Rossella D'Oria, Emanuele Carchia, Anna Leonardini, Angelo Cignarelli, Sebastio Perrini, Luigi Laviola, Francesco Giorgino
The effects of prolonged exposure of pancreatic β-cells to high saturated fatty acids on glucagon-like peptide-1 (GLP-1) action were investigated. Murine islets, human pancreatic 1.1B4 cells, and rat INS-1E cells were exposed to palmitate for 24 hours. mRNA and protein expression/phosphorylation were measured by real-time RT-PCR and immunoblotting, respectively. Specific short interfering RNAs were used to knockdown expression of the GLP-1 receptor (Glp1r) and Srebf1. Insulin release was assessed with a specific ELISA...
June 2016: Endocrinology
Jonas R Sanches, Lucas M França, Vinicyus T Chagas, Renato S Gaspar, Kayque A Dos Santos, Luciana M Gonçalves, Deborah M Sloboda, Alison C Holloway, Richard P Dutra, Everardo M Carneiro, Ana Paula G Cappelli, Antonio Marcus de A Paes
Syzygium cumini (L.) Skeels (Myrtaceae) has been traditionally used to treat a number of illnesses. Ethnopharmacological studies have particularly addressed antidiabetic and metabolic-related effects of extracts prepared from its different parts, especially seed, and pulp-fruit, however. there is a lack of studies on phytochemical profile and biological properties of its leaf. As there is considerable interest in bioactive compounds to treat metabolic syndrome and its clustered risk factors, we sought to characterize the metabolic effects of hydroethanolic extract of S...
2016: Frontiers in Pharmacology
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