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https://www.readbyqxmd.com/read/28108221/sirtuin-1-independent-effects-of-resveratrol-in-ins-1e-%C3%AE-cells
#1
Cihan S Erdogan, Mathias Mørup-Lendal, Louise T Dalgaard, Ole Vang
Resveratrol (Resv), a natural polyphenol, is suggested to have various health benefits including improved insulin sensitivity. Resv activates Sirtuin (Sirt1) in several species and tissues. Sirt1 is a protein deacetylase with an important role in ageing, metabolism and β-cell function. In insulinoma β-cells (INS-1E), Resv is previously shown to improve glucose-stimulated insulin secretion in a Sirt1-dependent mechanism and to protect against β-cell dedifferentiation in non-human primates, while inducing hypertrophy in myoblasts...
January 17, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28103285/radioiodinated-exendin-4-is-superior-to-the-radiometal-labelled-glucagon-like-peptide-1-receptor-probes-overcoming-their-high-kidney-uptake
#2
Tilman Läppchen, Roswitha Tönnesmann, Jos Eersels, Philipp T Meyer, Helmut R Maecke, Svetlana N Rylova
GLP-1 receptors are ideal targets for preoperative imaging of benign insulinoma and for quantifying the beta cell mass. The existing clinical tracers targeting GLP-1R are all agonists with low specific activity and very high kidney uptake. In order to solve those issues we evaluated GLP-1R agonist Ex-4 and antagonist Ex(9-39) radioiodinated at Tyr40 side by side with [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4 (68Ga-Ex-4) used in the clinic. The Kd, Bmax, internalization and binding kinetics of [Nle14,125I-Tyr40-NH2]Ex-4 and [Nle14,125I-Tyr40-NH2]Ex(9-39) were studied in vitro using Ins-1E cells...
2017: PloS One
https://www.readbyqxmd.com/read/28077579/neuron-enriched-rna-binding-proteins-regulate-pancreatic-beta-cell-function-and-survival
#3
Jon Agraves Juan-Mateu, Tatiana H Rech, Olatz Villate, Esther Lizarraga-Mollinedo, Anna Wendt, Jean-Valery Turatsinze, Leticia A Brondani, Tarlliza R Nardelli, Tatiane C Nogueira, Jonatan L S Esguerra, Maria In Ecircs Alvelos, Piero Marchetti, Lena Eliasson, D Eacutecio L Eizirik
Pancreatic beta cell failure is the central event leading to diabetes. Beta cells share many phenotypic traits with neurons, and proper beta cell function relies on the activation of several neuronal-like transcription programs. Regulation of gene expression by alternative splicing plays a pivotal role in brain, where it affects neuronal development, function and disease. The role of alternative splicing in beta cells remains unclear, but recent data indicate that splicing alterations modulated by both inflammation and susceptibility genes for diabetes contribute to beta cell dysfunction and death...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28012278/the-physiological-effects-of-dandelion-taraxacum-officinale-in-type-2-diabetes
#4
Fonyuy E Wirngo, Max N Lambert, Per B Jeppesen
The tremendous rise in the economic burden of type 2 diabetes (T2D) has prompted a search for alternative and less expensive medicines. Dandelion offers a compelling profile of bioactive components with potential anti-diabetic properties. The Taraxacum genus from the Asteraceae family is found in the temperate zone of the Northern hemisphere. It is available in several areas around the world. In many countries, it is used as food and in some countries as therapeutics for the control and treatment of T2D. The anti-diabetic properties of dandelion are attributed to bioactive chemical components; these include chicoric acid, taraxasterol (TS), chlorogenic acid, and sesquiterpene lactones...
July 2016: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28011945/orexin-a-modulates-ins-1e-cell-proliferation-and-insulin-secretion-via-extracellular-signal-regulated-kinase-and-transient-receptor-potential-channels
#5
M Skrzypski, N Khajavi, S Mergler, M Billert, D Szczepankiewicz, T Wojciechowicz, K W Nowak, M Z Strowski
Orexins A (OXA) and B (OXB) control energy homeostasis by regulating food intake, energy expenditure and sleep-wake cycle. Several studies showed that OXA stimulates insulin secretion and proliferation of beta cells. However, mechanisms of action are still not well understood. Here, we investigated whether ERK and transient receptor potential channels (TRPs) play a role in mediating the effect of OXA on cell growth, insulin production, and secretion using the established INS-1E cell line. Cell proliferation was measured using BrdU assay...
October 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28004151/reciprocal-regulation-of-mtor-complexes-in-pancreatic-islets-from-humans-with-type-2-diabetes
#6
Ting Yuan, Sahar Rafizadeh, Kanaka Durga Devi Gorrepati, Blaz Lupse, Jose Oberholzer, Kathrin Maedler, Amin Ardestani
AIMS/HYPOTHESIS: Mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of nutritional status at the cellular and organismic level. While mTORC1 mediates beta cell growth and expansion, its hyperactivation has been observed in pancreatic islets from animal models of type 2 diabetes and leads to beta cell loss. We sought to determine whether such mTORC1 activation occurs in humans with type 2 diabetes or in metabolically stressed human islets and whether mTORC1 blockade can restore beta cell function of diabetic islets...
December 21, 2016: Diabetologia
https://www.readbyqxmd.com/read/27995762/encapsulation-of-insulin-secreting-cells-expressing-a-genetically-encoded-fluorescent-calcium-indicator-for-cell-based-sensing-in-vivo
#7
Christophe Boss, Umberto De Marchi, Aurélie Hermant, Mouna Conrad, Federico Sizzano, Alessio Palini, Andreas Wiederkehr, Nicolas Bouche
The development of cell-based biosensors that give insight into cell and tissue function in vivo is an attractive technology for biomedical research. Here, the development of a cell line expressing a fluorescent calcium sensor for the study of beta-cell function in vivo is reported. The bioresponsive cell model is based on INS-1E pancreatic beta-cells, stably expressing the genetically encoded cameleon-based fluorescent sensor YC3.6cyto . Following single-cell selection and expansion, functional testing and in vitro encapsulation experiments are used to identify a suitable clone of INS-1E cells expressing the calcium sensor...
December 20, 2016: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27989965/st-john-s-wort-extract-and-hyperforin-inhibit-multiple-phosphorylation-steps-of-cytokine-signaling-and-prevent-inflammatory-and-apoptotic-gene-induction-in-pancreatic-%C3%AE-cells
#8
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
https://www.readbyqxmd.com/read/27980130/insulinotropic-effects-of-gpr120-agonists-are-altered-in-obese-diabetic-and-obese-non-diabetic-states
#9
Dan Zhang, Wing Yan So, Yi Wang, Shang Ying Wu, Qianni Cheng, Po Sing Leung
G-protein-coupled receptor 120 (GPR120) is a putative target for obesity and diabetes therapies. However, it remains controversial whether resident GPR120 plays a direct regulatory role in islet β-cell insulin secretion. The present study examined this issue in isolated rodent islets and rat β-cell line INS-1E, and assessed the role of GPR120 in islet insulin secretion in obese non-diabetic (OND) and diabetic states. GPR120 expression was detected in rodent islet β-cells. Docosahexaenoic acid (DHA) and synthetic GPR120 agonist GSK137647 (GSK) augmented insulin release from rat/mouse islets and INS-1E; DHA effects were partially mediated by GPR40...
February 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27927723/coordinated-activation-of-mitochondrial-respiration-and-exocytosis-mediated-by-pkc-signaling-in-pancreatic-%C3%AE-cells
#10
Jaime Santo-Domingo, Isabelle Chareyron, Loïc Dayon, Antonio Núñez Galindo, Ornella Cominetti, María Pilar Giner Giménez, Umberto De Marchi, Carles Canto, Martin Kussmann, Andreas Wiederkehr
Mitochondria play a central role in pancreatic β-cell nutrient sensing by coupling their metabolism to plasma membrane excitability and insulin granule exocytosis. Whether non-nutrient secretagogues stimulate mitochondria as part of the molecular mechanism to promote insulin secretion is not known. Here, we show that PKC signaling, which is employed by many non-nutrient secretagogues, augments mitochondrial respiration in INS-1E (rat insulinoma cell line clone 1E) and human pancreatic β-cells. The phorbol ester, phorbol 12-myristate 13-acetate, accelerates mitochondrial respiration at both resting and stimulatory glucose concentrations...
December 7, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27797297/resistin-is-produced-by-rat-pancreatic-islets-and-regulates-insulin-and-glucagon-in-vitro-secretion
#11
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...
November 2016: Islets
https://www.readbyqxmd.com/read/27780755/st-john-s-wort-extract-and-hyperforin-inhibit-multiple-phosphorylation-steps-of-cytokine-signaling-and-prevent-inflammatory-and-apoptotic-gene-induction-in-pancreatic-%C3%AE-cells
#12
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...
December 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27684962/cytosolic-delivery-of-nanolabels-prevents-their-asymmetric-inheritance-and-enables-extended-quantitative-in-vivo-cell-imaging
#13
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
https://www.readbyqxmd.com/read/27645309/polygodial-a-sesquiterpene-isolated-from-drimys-brasiliensis-winteraceae-triggers-glucocorticoid-like-effects-on%C3%A2-pancreatic%C3%A2-%C3%AE-cells
#14
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
https://www.readbyqxmd.com/read/27631977/cytosolic-and-calcium-independent-phospholipases-a2-activation-and-prostaglandins-e2-are-associated-with-escherichia-coli-induced-reduction-of-insulin-secretion-in-ins-1e-cells
#15
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
https://www.readbyqxmd.com/read/27568038/20-hete-attenuates-the-response-of-glucose-stimulated-insulin-secretion-through-the-akt-gsk-3%C3%AE-glut2-pathway
#16
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
https://www.readbyqxmd.com/read/27565711/intracellular-alkalinization-by-phosphate-uptake-via-type-iii-sodium-phosphate-cotransporter-participates-in-high-phosphate-induced-mitochondrial-oxidative-stress-and-defective-insulin-secretion
#17
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
https://www.readbyqxmd.com/read/27563695/chronic-exposure-to-proline-causes-aminoacidotoxicity-and-impaired-beta-cell-function-studies-in-vitro
#18
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
https://www.readbyqxmd.com/read/27545881/integrative-genomics-outlines-a-biphasic-glucose-response-and-a-chrebp-ror%C3%AE-axis-regulating-proliferation-in-%C3%AE-cells
#19
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
https://www.readbyqxmd.com/read/27539450/single-fluorescent-protein-based-indicators-for-zinc-ion-zn-2
#20
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
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