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Pancreas beta cells

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https://www.readbyqxmd.com/read/28551699/the-role-of-somatostatin-in-glp-1-induced-inhibition-of-glucagon-secretion-in-mice
#1
Anne Ørgaard, Jens J Holst
AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) receptor agonists are currently used for the treatment of type 2 diabetes. Their main mechanism of action is enhancement of glucose-induced insulin secretion (from increased beta cell glucose sensitivity) and inhibition of glucagon secretion. The latter has been demonstrated to account for about half of their blood glucose-lowering activity. Whereas the effect of GLP-1 on insulin secretion is clearly dependent on ambient glucose concentrations and has been described in detail, the mechanism responsible for the inhibitory effect of GLP-1 on glucagon secretion is heavily debated...
May 27, 2017: Diabetologia
https://www.readbyqxmd.com/read/28535085/characterization-of-an-encapsulated-insulin-secreting-human-pancreatic-beta-cell-line-in-a-modular-microfluidic-device
#2
Argia Acarregui, Jesús Ciriza, Laura Saenz Del Burgo, Haritz Gurruchaga, José Yeste, Xavier Illa, Gorka Orive, Rosa M Hernández, Rosa Villa, Jose Luis Pedraz
Type I diabetes mellitus is characterized by the destruction of the insulin producing beta cells within the pancreas by the immune system. After the success of Edmonton protocol, islet transplantation has shown to be a promising therapy, but with the Achilles´ heel of the need of using immunosuppressive drugs. Currently, cell encapsulation technology represents a real alternative to protect transplanted islets from the host´s immune attack. Although preliminary in vitro studies with encapsulated cells have been traditionally performed under static conditions in terms of viability and efficiency, these static cultures do not represent a close approach to in vivo environments...
May 23, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28525974/pancreas-and-gallbladder-agenesis-in-a-newborn-with-semilobar-holoprosencephaly-a-case-report
#3
Robert Hilbrands, Kathelijn Keymolen, Alex Michotte, Miriam Marichal, Filip Cools, Anieta Goossens, Peter In't Veld, Jean De Schepper, Andrew Hattersley, Harry Heimberg
BACKGROUND: Pancreatic agenesis is an extremely rare cause of neonatal diabetes mellitus and has enabled the discovery of several key transcription factors essential for normal pancreas and beta cell development. CASE PRESENTATION: We report a case of a Caucasian female with complete pancreatic agenesis occurring together with semilobar holoprosencephaly (HPE), a more common brain developmental disorder. Clinical findings were later confirmed by autopsy, which also identified agenesis of the gallbladder...
May 19, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28504695/epigenetic-pathway-inhibitors-represent-potential-drugs-for-treating-pancreatic-and-bronchial-neuroendocrine-tumors
#4
K E Lines, M Stevenson, P Filippakopoulos, S Müller, H E Lockstone, B Wright, S Grozinsky-Glasberg, A B Grossman, S Knapp, D Buck, C Bountra, R V Thakker
Cancer is associated with alterations in epigenetic mechanisms such as histone modifications and methylation of DNA, and inhibitors targeting epigenetic mechanisms represent a novel class of anti-cancer drugs. Neuroendocrine tumors (NETs) of the pancreas (PNETs) and bronchus (BNETs), which may have 5-year survivals of <50% and as low as 5%, respectively, represent targets for such drugs, as >40% of PNETs and ~35% of BNETs have mutations of the multiple endocrine neoplasia type 1 (MEN1) gene, which encodes menin that modifies histones by interacting with histone methyltransferases...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28504618/butyrate-reduces-high-fat-diet-induced-metabolic-alterations-hepatic-steatosis-and-pancreatic-beta-cell-and-intestinal-barrier-dysfunctions-in-prediabetic-mice
#5
V A Matheus, Lcs Monteiro, R B Oliveira, D A Maschio, C B Collares-Buzato
In this study, we investigated the effect of diet supplementation with sodium butyrate (5% w/w), a short-chain fatty acid produced by the intestinal microbiota, on metabolic parameters, body adiposity, hepatic and pancreatic lipid accumulation, beta cell function/mass as well as on the structure and function of the tight junction-mediated intestinal epithelial barrier in both normal and obese/prediabetic C57 mice fed a regular (control) or high-fat diet for 60 days, respectively. Butyrate treatment significantly inhibited all the high-fat-induced metabolic dysfunctions evaluated, i...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28496188/preclinical-evaluation-of-pac1-targeting-with-radiolabeled-maxadilan
#6
Lieke Joosten, Maarten Brom, Martin K H Schäfer, Otto C Boerman, Eberhard Weihe, Martin Gotthardt
There is an ongoing search for new tracers to optimize imaging of beta cell-derived tumors (insulinomas). The PAC1 receptor, expressed by insulinomas, can be used for targeting of these tumors. Here, we investigated whether radiolabeled maxadilan could be used for insulinoma imaging. Maxadilan was C- or N-terminally conjugated with DTPA (termed maxadilan-DPTA or DTPA-maxadilan respectively). BALB/c nude mice bearing subcutaneous INS-1 tumors were injected with either In-111-labeled maxadilan-DTPA or In-111-DTPA-maxadilan...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28489277/pancreas-after-islet-pai-transplantation-in-non-uremic-type-1-diabetes-a-strategy-for-restoring-durable-insulin-independence
#7
S A Wisel, J M Gardner, G R Roll, J Harbell, C E Freise, S Feng, S M Kang, R Hirose, D B Kaufman, A Posselt, P G Stock
Islet transplantation offers a minimally-invasive approach for beta cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet re-infusions from distinct donors, thus increasing the risk for allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the US. However, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28466634/update-on-pancreatic-transplantation-on-the-management-of-diabetes
#8
Carlo Lombardo, Vittorio G Perrone, Gabriella Amorese, Fabio Vistoli, Walter Baronti, Piero Marchetti, Ugo Boggi
Pancreas transplantation is the only therapy that can restore insulin independence in beta-cell penic diabetic recipients. Because of the need for life-long immunosuppression and the intial surgical risk associated with the transplant procedure, Pancreas transplantation is a therapeutic option only in selected diabetic patients. Based on renal function, three main populations of diabetic recipients of a pancreas transplant can be identified: uremic patients, post-uremic patients (following successful kidney transplantation), and non-uremic patients...
May 2, 2017: Minerva Medica
https://www.readbyqxmd.com/read/28438671/alkaline-ph-induces-irr-mediated-phosphorylation-of-irs-1-and-actin-cytoskeleton-remodeling-in-a-pancreatic-beta-cell-line
#9
Igor E Deyev, Nadezhda V Popova, Oxana V Serova, Svetlana V Zhenilo, Marì Regoli, Eugenio Bertelli, Alexander G Petrenko
Secretion of mildly alkaline (pH 8.0-8.5) juice to intestines is one of the key functions of the pancreas. Recent reports indicate that the pancreatic duct system containing the alkaline juice may adjoin the endocrine cells of pancreatic islets. We have previously identified the insulin receptor-related receptor (IRR) that is expressed in islets as a sensor of mildly alkaline extracellular media. In this study, we show that those islet cells that are in contact with the excretory ducts are also IRR-expressing cells...
April 21, 2017: Biochimie
https://www.readbyqxmd.com/read/28422431/effect-of-empagliflozin-on-tacrolimus-induced-pancreas-islet-dysfunction-and-renal-injury
#10
J Jin, L Jin, K Luo, S W Lim, B H Chung, C W Yang
An inhibitor of sodium glucose co-transporter type 2 (SGLT-2) is recommended in type 2 diabetes mellitus (DM) but its use is still undetermined in tacrolimus (TAC)-induced DM. We evaluated the effect of empagliflozin (Em) on TAC-induced pancreatic islet dysfunction and renal injury in an experimental model of TAC-induced DM and in vitro. TAC induced a twofold increase in SGLT-2 expression, while Em decreased SGLT-2 expression and further increased urinary glucose excretion compared to the TAC group. Em reduced hyperglycemia and increased plasma insulin level, pancreatic islet size, and glucose-stimulated insulin secretion compared to the TAC group...
April 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28419211/the-inhibitory-g-protein-%C3%AE-subunit-g%C3%AE-z-promotes-type-1-diabetes-like-pathophysiology-in-nod-mice
#11
Rachel J Fenske, Mark T Cadena, Quincy E Harenda, Haley N Wienkes, Kathryn Carbajal, Michael D Schaid, Erin Laundre, Allison L Brill, Nathan A Truchan, Harpreet Brar, Jaclyn Wisinski, Jinjin Cai, Timothy E Graham, Feyza Engin, Michelle E Kimple
The alpha subunit of the heterotrimeric Gz protein, Gαz, promotes beta-cell death and inhibits beta-cell replication when pancreatic islets are challenged by stressors. Thus, we hypothesized that loss of Gαz protein would preserve functional beta-cell mass in the non-obese diabetic (NOD) model, protecting from overt diabetes. We saw that protection from diabetes was robust and durable up to 35 weeks of age in Gαz knockout mice. By 17 weeks of age, Gαz-null NOD mice had significantly higher diabetes-free survival than wild-type littermates...
April 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28405576/evaluation-of-anti-diabetic-activity-of-ahpl-aytab-0513-tablet-in-streptozotocin-induced-diabetes-in-rats
#12
Sanjay U Nipanikar, Soham S Chitlange, Dheeraj Nagore
BACKGROUND: Diabetes is a chronic, progressive disease associated with several complications leading to significant mortality and morbidity. Limitations and drawbacks of the conventional treatment generate need for safer, effective complimentary therapies to prevent complications, and maintain normoglycemic status. AIM AND OBJECTIVES: The aim of this study is to to evaluate antidiabetic activity of AHPL/AYTAB/0513 tablet alone, oral hypoglycemic agents (OHA[s]), and combination of AHPL/AYTAB/0513 tablet and OHA(s) in streptozotocin-induced diabetes in rats...
January 2017: International Journal of Pharmaceutical Investigation
https://www.readbyqxmd.com/read/28393070/assessment-of-toxicological-perturbations-and-variants-of-pancreatic-islet-development-in-the-zebrafish-model
#13
Karilyn E Sant, Haydee M Jacobs, Jiali Xu, Katrina A Borofski, Larry G Moss, Jennifer B Moss, Alicia R Timme-Laragy
The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology. Disruption of development by toxicants can alter cell fate and migration, resulting in structural alterations that are difficult to detect in mammalian embryo systems, but that are easily observed in the zebrafish embryo model (Danio rerio)...
September 2016: Toxics
https://www.readbyqxmd.com/read/28380361/efficient-generation-of-glucose-responsive-beta-cells-from-isolated-gp2-human-pancreatic-progenitors
#14
Jacqueline Ameri, Rehannah Borup, Christy Prawiro, Cyrille Ramond, Karen A Schachter, Raphael Scharfmann, Henrik Semb
Stem cell-based therapy for type 1 diabetes would benefit from implementation of a cell purification step at the pancreatic endoderm stage. This would increase the safety of the final cell product, allow the establishment of an intermediate-stage stem cell bank, and provide a means for upscaling β cell manufacturing. Comparative gene expression analysis revealed glycoprotein 2 (GP2) as a specific cell surface marker for isolating pancreatic endoderm cells (PECs) from differentiated hESCs and human fetal pancreas...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28365524/pancreas-and-liver-uptake-of-new-radiolabeled-incretins-glp-1-and-exendin-4-in-models-of-diet-induced-and-diet-restricted-obesity
#15
Daniele Seo, Bluma Linkowski Faintuch, Erica Aparecida de Oliveira, Joel Faintuch
INTRODUCTION: Radiolabeled GLP-1 and its analog Exendin-4, have been employed in diabetes and insulinoma. No protocol in conventional Diet-Induced Obesity (DIO), and Diet-Restricted Obesity (DRO), has been identified. Aiming to assess pancreatic beta cell uptake in DIO and DRO, a protocol was designed. METHODS: GLP-1-βAla-HYNIC and HYNIC-βAla-Exendin-4 were labeled with technetium-99m. Four Swiss mouse models were adopted: Controls (C), Alloxan Diabetes Controls (ADC), DIO and DRO...
June 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28362046/co-microencapsulation-of-bmscs-and-mouse-pancreatic-%C3%AE-cells-for-improving-the-efficacy-of-type-i-diabetes-therapy
#16
Ruimin Long, Yuangang Liu, Shibin Wang, Li Ye, Peng He
INTRODUCTION: To overcome the shortcomings of pancreas transplantation and insulin injection treatment for type I diabetes, biocompatible materials were used to prepare alginate-chitosan-alginate microcapsules that co-encapsulated bone marrow mesenchymal stem cells and mouse pancreatic β cells to treat diabetic mice. METHODS: Blank alginate-chitosan-alginate (ACA) microcapsules and co-microencapsulated cells were prepared using a high-voltage electrostatic method and then characterized using an inverted microscope...
May 9, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28346693/using-a-novel-nqo1-bioactivatable-drug-beta-lapachone-arq761-to-enhance-chemotherapeutic-effects-by-metabolic-modulation-in-pancreatic-cancer
#17
Muhammad Shaalan Beg, Xiumei Huang, Molly A Silvers, David E Gerber, Joyce Bolluyt, Venetia Sarode, Farjana Fattah, Ralph J Deberardinis, Matthew E Merritt, Xian-Jin Xie, Richard Leff, Daniel Laheru, David A Boothman
Novel, tumor-selective therapies are needed to increase the survival rate of pancreatic cancer patients. K-Ras-mutant-driven NAD(P)H:quinone oxidoreductase 1 (NQO1) is over-expressed in pancreatic tumor versus associated normal tissue, while catalase expression is lowered compared to levels in associated normal pancreas tissue. ARQ761 undergoes a robust, futile redox cycle in NQO1+ cancer cells, producing massive hydrogen peroxide (H2 O2 ) levels; normal tissues are spared by low NQO1 and high catalase expression...
March 27, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28343084/role-of-pterostilbene-in-attenuating-immune-mediated-devastation-of-pancreatic-beta-cells-via-nrf2-signaling-cascade
#18
Dornadula Sireesh, Munuswamy-Ramanujam Ganesh, Umapathy Dhamodharan, Murugesan Sakthivadivel, Srinivasan Sivasubramanian, Palani Gunasekaran, Kunka Mohanram Ramkumar
Nrf2 (nuclear factor erythroid 2-related factor-2) is a transcription factor that regulates oxidative/xenobiotic stress response and also suppress inflammation. Nrf2 signaling is associated with an increased susceptibility to various kinds of stress. Nrf2 has been shown as a promising therapeutic target in various human diseases including diabetes. Our earlier studies showed Pterostilbene (PTS) as a potent Nrf2 activator, and it protects the pancreatic β-cells against oxidative stress. In this study, we investigated PTS confer protection against cytokine-induced β-cell apoptosis and its role on insulin secretion in streptozotocin (STZ)-induced diabetic mice...
June 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28342091/both-nicotine-reward-and-withdrawal-are-enhanced-in-a-rodent-model-of-diabetes
#19
Joseph A Pipkin, Bryan Cruz, Rodolfo J Flores, Cecilia A Hinojosa, Luis M Carcoba, Melissa Ibarra, Wendy Francis, Arbi Nazarian, Laura E O'Dell
RATIONALE: It is presently unclear whether diabetic rats experience greater rewarding effects of nicotine and/or negative affective states produced by nicotine withdrawal. OBJECTIVE: The present study utilized a rodent model of diabetes to examine the rewarding effects of nicotine and negative affective states and physical signs produced by withdrawal. METHODS: Separate groups of rats received systemic administration of either vehicle or streptozotocin (STZ), which destroys insulin-producing beta cells in the pancreas and elevates glucose levels...
May 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28327131/transcriptome-analysis-of-pancreatic-cells-across-distant-species-highlights-novel-important-regulator-genes
#20
Estefania Tarifeño-Saldivia, Arnaud Lavergne, Alice Bernard, Keerthana Padamata, David Bergemann, Marianne L Voz, Isabelle Manfroid, Bernard Peers
BACKGROUND: Defining the transcriptome and the genetic pathways of pancreatic cells is of great interest for elucidating the molecular attributes of pancreas disorders such as diabetes and cancer. As the function of the different pancreatic cell types has been maintained during vertebrate evolution, the comparison of their transcriptomes across distant vertebrate species is a means to pinpoint genes under strong evolutionary constraints due to their crucial function, which have therefore preserved their selective expression in these pancreatic cell types...
March 21, 2017: BMC Biology
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