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https://www.readbyqxmd.com/read/28109023/intraportal-islet-transplantation-the-impact-of-the-liver-micro-environment
#1
REVIEW
Vaihere Delaune, Thierry Berney, Stéphanie Lacotte, Christian Toso
The portal vein remains the preferred site for pancreatic islet transplantation due to its easy access and low morbidity. However, despite great progress in isolation and transplantation protocols over the past few years, it is still associated with the early loss of some 50-70% of transplanted islets. The complex liver micro-environment itself presumably plays an important role in this loss. The present review focuses on the specifics of the liver micro-environment, notably the localized hepatic ischemia/reperfusion injury following transplantation, the low oxygenation of the portal vein, the instant blood mediated inflammatory reaction (IBMIR), the endogenous liver immune system, and the gut-liver axis, and how they can each have an impact on the transplanted islets...
January 21, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28107503/osteopontin-affects-insulin-vesicle-localization-and-ca2-homeostasis-in-pancreatic-beta-cells-from-female-mice
#2
Anna Wendt, Inês G Mollet, Anki Knutsson, Victor S Bolmgren, Anna Hultgårdh-Nilsson, Maria F Gomez, Lena Eliasson
Type 2 diabetic patients suffer from insulin resistance and reduced insulin secretion. Osteopontin (OPN), a versatile protein expressed in several tissues throughout the body including the islets of Langerhans, has previously been implicated in the development of insulin resistance. Here we have investigated the role of OPN in insulin secretion using an OPN knock out mouse model (OPN-/-). Ultra-structural analyzes of islets from OPN-/- and WT mice indicated weaker cell-cell connections between the islet cells in the OPN-/- mouse compared to WT...
2017: PloS One
https://www.readbyqxmd.com/read/28101570/inhibition-of-tlr4-protects-rat-islets-against-lipopolysaccharide-induced-dysfunction
#3
Xiao Wang, Qin Min Ge, Fan Bian, Yan Dong, Chun Mei Huang
Oxidative stress leads to dysfunction in pancreatic cells, causing a reduction in insulin secretion following exposure to glucose. Toll-like receptor 4 (TLR4) may be activated by exposure to lipopolysaccharide (LPS) stress. TLR4 may mediate the initiation of inflammatory and immune defense responses; however, the importance of the LPS/TLR4 interaction in apoptosis induced by oxidative stress in pancreatic β cells remains to be elucidated. The present study aimed to investigate the importance of TLR4 during LPS‑induced oxidative stress, apoptosis and dysfunction of insulin secretion in isolated islets of rats...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28100871/in-vivo-direct-reprogramming-of-liver-cells-to-insulin-producing-cells-by-virus-free-overexpression-of-defined-factors
#4
Xiao-Fei Yang, Li-Wei Ren, Lu Yang, Chun-Yan Deng, Fu-Rong Li
Direct reprogramming of autologous cells from diabetes patients to insulin producing cells is a new method for pancreatic cell replacement therapy. At present, transdifferentiation among mature cells is achieved mainly by introducing foreign genes into the starting tissue with viral vector, but there are potentical safety problems. In the present study, we delivered plasmids carrying Pdx1, Neurog3 and MafA genes (PNM) into mouse hepatocytes by hydrodynamics tail vein injection, investigated islet β cells markers in transfected cells from protein and mRNA level, and then observed the long-term control of blood glucose in diabetic mice...
January 18, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28100774/loss-of-cyclin-dependent-kinase-2-in-the-pancreas-links-primary-%C3%AE-cell-dysfunction-to-progressive-depletion-of-%C3%AE-cell-mass-and-diabetes
#5
So Yoon Kim, Ji-Hyeon Lee, Matthew J Merrins, Oksana Gavrilova, Xavier Bisteau, Philipp Kaldis, Leslie S Satin, Sushil G Rane
The failure of pancreatic islet β-cells is a major contributor to the etiology of Type 2 diabetes. β-cell dysfunction and declining β-cell mass are two mechanisms that contribute to this failure, although it is unclear if they are molecularly linked. Here, we show that the cell cycle regulator, cyclin-dependent kinase 2 (Cdk2), couples primary β-cell dysfunction to the progressive deterioration of β-cell mass in diabetes. Mice with pancreas-specific deletion of Cdk2 are glucose intolerant primarily due to defects in glucose-stimulated insulin secretion...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100476/chronic-anemic-hypoxemia-attenuates-glucose-stimulated-insulin-secretion-in-fetal-sheep
#6
Joshua S Benjamin, Christine B Culpepper, Laura D Brown, Stephanie R Wesolowski, Sonnet S Jonker, Melissa Ann Davis, Sean W Limesand, Randall B Wilkening, William W Hay, Paul J Rozance
Fetal insulin secretion is inhibited by acute hypoxemia. The relationship between prolonged hypoxemia and insulin secretion, however, is less well defined. To test the hypothesis that prolonged fetal hypoxemia impairs insulin secretion, studies were performed in sheep fetuses that were bled to anemic conditions for 9 ± 0 days (anemic, n=19) and compared to control fetuses (n=15). Arterial hematocrit and oxygen content were 34% and 52% lower, respectively, in anemic vs. control fetuses (P<0.0001). Plasma glucose concentrations were 21% higher in the anemic group (P<0...
January 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28099262/angiotensin-ii-type-2-receptor-activation-with-compound-21-augments-islet-function-and-regeneration-in-streptozotocin-induced-neonatal-rats-and-human-pancreatic-progenitor-cells
#7
Lin Wang, Yi Wang, Xing Yu Li, Po Sing Leung
OBJECTIVES: We investigated the effects of compound 21 (C21), a nonpeptide angiotensin II type 2 receptor agonist, on islet cell function and survival in streptozotocin (STZ)-treated neonatal rats and human pancreatic progenitor cells. METHODS: Neonatal rats were randomized into 5 groups, including a control, an STZ (100 mg/kg, intraperitoneally), and 3 STZ + C21 (0.25, 0.5, and 1 mg/kg per day for 7 days, intraperitoneally) groups. Body weight and blood glucose were monitored daily...
January 18, 2017: Pancreas
https://www.readbyqxmd.com/read/28099206/is-a-%C3%AE-cell-a-%C3%AE-cell
#8
Chaoxing Yang, Feorillo Galivo, Craig Dorrell
PURPOSE OF REVIEW: This report examines recent publications identifying phenotypic and functional heterogeneity among pancreatic β cells and investigating their potential roles in normal and abnormal islet function. The development of new methods and tools for the study of individual islet cells has produced a surge of interest in this topic. RECENT FINDINGS: Studies of β cell maturation and pregnancy-induced proliferation have identified changes in serotonin and transcription factors SIX2/3 expression as markers of temporal heterogeneity...
January 17, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28098903/vitexin-alleviates-lipopolysaccharide%C3%A2-induced-islet-cell-injury-by-inhibiting-hmgb1-release
#9
Feifei Wang, Jiajing Yin, Yujin Ma, Hongwei Jiang, Yanbo Li
Diabetes mellitus (DM) is a chronic metabolic disease, where the predominant pathogenesis is pancreatic β‑cells dysfunction or injury. It has been well established that inflammation leads to a gradual exhaustion of pancreatic β‑cell function with decreased β‑cell mass likely resulting from pancreatic β‑cells apoptosis or death. Vitexin, a major bioactive flavonoid compound in plants has numerous pharmacological properties, including antioxidant, anti‑inflammatory and antimyeloperoxidase. Whether vitexin can protect pancreatic β‑cells against lipopolysaccharide (LPS)‑induced pro‑inflammatory cytokine production and apoptosis has received little attention...
January 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28098405/shielding-engineered-islets-with-mesenchymal-stem-cells-enhance-survival-under-hypoxia
#10
Bhawna Chandravanshi, Ramesh Ramchandra Bhonde
In the present study we focused on the improvisation of islet survival in hypoxia.The Islet like cell aggregates (ICAs) derived from wharton's jelly mesenchymal stem cells (WJ MSC) were cultured with and without WJ MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin,Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitated highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay...
January 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28097390/a-role-of-plc-pkc-dependent-pathway-in-glp-1-stimulated-insulin-secretion
#11
REVIEW
Makoto Shigeto, Chae Young Cha, Patrik Rorsman, Kohei Kaku
Glucagon-like peptide-1 (GLP-1) is an endogenous glucose-lowering hormone and GLP-1 receptor agonists are currently being used as antidiabetic drugs clinically. The canonical signalling pathway (including cAMP, Epac2, protein kinase A (PKA) and KATP channels) is almost universally accepted as the main mechanism of GLP-1-stimulated insulin secretion. This belief is based on in vitro studies that used nanomolar (1-100 nM) concentrations of GLP-1. Recently, it was found that the physiological concentrations (1-10 pM) of GLP-1 also stimulate insulin secretion from isolated islets, induce membrane depolarization and increase of intracellular [Ca(2+)] in isolated β cells/pancreatic islets...
January 17, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28097011/a-selective-gpr40-ffar1-agonist-ly2881835-provides-immediate-and-durable-glucose-control-in-rodent-models-of-type-2-diabetes
#12
Yanyun Chen, Min Song, Jonathan P Riley, Charlie C Hu, Xianbu Peng, Donalyn Scheuner, Krister Bokvist, Pranab Maiti, Steven D Kahl, Chahrzad Montrose-Rafizadeh, Chafiq Hamdouchi, Anne Reifel Miller
LY2881835 is a selective, potent, and efficacious GPR40 agonist. The objective of the studies described here was to examine the pharmacological properties of LY2881835 in preclinical models of T2D. Significant increases in insulin secretion were detected when LY2881835 was tested in primary islets from WT mice but not in islets from GPR40 KO mice. Furthermore, LY2881835 potentiated glucose stimulated insulin secretion in normal lean mice. Acute administration of LY2881835 lowered glucose during OGTTs in WT mice but not in GPR40 KO mice...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28094469/immunohistochemical-assessment-of-glucagon-like-peptide-1-receptor-glp-1r-expression-in-the-pancreas-of-patients-with-type-2-diabetes
#13
Rikke Kaae Kirk, Charles Pyke, Matthias G von Herrath, Jane Preuss Hasselby, Lars Pedersen, Pia Gottrup Mortensen, Lotte Bjerre Knudsen, Ken Coppieters
Glucagon-like peptide-1 (GLP-1) is an incretin hormone which stimulates insulin release and inhibits glucagon secretion from the pancreas in a glucose-dependent manner. Incretin-based therapies, consisting of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are used for the treatment of T2D. Immunohistochemical studies for GLP-1R expression have previously been hampered by the use of unspecific polyclonal antibodies. This study used a new monoclonal antibody to assess GLP-1R expression in pancreatic tissue from 23 patients with T2D, including 7 with a DPP-4 inhibitor and 1 with a GLP-1R agonist treatment history...
January 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28089906/adenosine-signaling-in-diabetes-mellitus-and-associated-cardiovascular-and-renal-complications
#14
REVIEW
Maria Peleli, Mattias Carlstrom
Diabetes mellitus is characterized by abnormal glucose and lipid metabolism, and subsequent hyperglycemia and dyslipidemia, which results from defects in pancreatic beta islets insulin secretion and/or decreased insulin sensitivity in metabolically active organs (i.e. liver, skeletal muscle and adipose tissue). Accumulating evidence highlights a critical role for the adenosine system in the regulation of insulin and glucose homeostasis and the pathophysiology of type 2 diabetes (T2D). Adenosine is a key diverse extracellular signaling molecule that regulates several aspects of tissue function by activating four G-protein-coupled receptors (i...
January 12, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28089828/nitrite-increases-glucose-stimulated-insulin-secretion-and-islet-insulin-content-in-obese-type-2-diabetic-male-rats
#15
Sevda Gheibi, Fatemeh Bakhtiarzadeh, Sajad Jeddi, Khadijeh Farrokhfall, Homeira Zardooz, Asghar Ghasemi
PURPOSE: Reduced bioavailability of nitric oxide (NO) is associated with pathogenesis of type 2 diabetes. Nitrite can act as a substrate for generation of systemic NO. The aim of this study was to examine the effects of nitrite administration on glucose-stimulated insulin secretion (GSIS) and islet insulin content in obese type 2 diabetic rats. METHODS: Male rats were divided into 4 groups: Control, control + nitrite, diabetes, and diabetes + nitrite. Sodium nitrite (50 mg/L in drinking water) was administered for 8 weeks...
January 9, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28078386/early-differences-in-islets-from-prediabetic-nod-mice-combined-microarray-and-proteomic-analysis
#16
Inne Crèvecoeur, Valborg Gudmundsdottir, Saurabh Vig, Fernanda Marques Câmara Sodré, Wannes D'Hertog, Ana Carolina Fierro, Leentje Van Lommel, Conny Gysemans, Kathleen Marchal, Etienne Waelkens, Frans Schuit, Søren Brunak, Lut Overbergh, Chantal Mathieu
AIMS/HYPOTHESIS: Type 1 diabetes is an endocrine disease where a long preclinical phase, characterised by immune cell infiltration in the islets of Langerhans, precedes elevated blood glucose levels and disease onset. Although several studies have investigated the role of the immune system in this process of insulitis, the importance of the beta cells themselves in the initiation of type 1 diabetes is less well understood. The aim of this study was to investigate intrinsic differences present in the islets from diabetes-prone NOD mice before the onset of insulitis...
January 12, 2017: Diabetologia
https://www.readbyqxmd.com/read/28078385/glucose-and-fatty-acids-synergistically-and-reversibly-promote-beta-cell-proliferation-in-rats
#17
Valentine S Moullé, Kevin Vivot, Caroline Tremblay, Bader Zarrouki, Julien Ghislain, Vincent Poitout
AIMS/HYPOTHESIS: The mechanisms underlying pancreatic islet mass expansion have attracted considerable interest as potential therapeutic targets to prevent or delay the onset of type 2 diabetes. While several factors promoting beta cell proliferation have been identified, in the context of nutrient excess the roles of glucose or NEFA in relation to insulin resistance remain unclear. Here we tested the hypothesis that glucose and NEFA synergistically and reversibly promote beta cell proliferation in the context of nutrient-induced insulin resistance...
January 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28077579/neuron-enriched-rna-binding-proteins-regulate-pancreatic-beta-cell-function-and-survival
#18
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/28077129/hypoglycemic-and-pancreatic-protective-effects-of-portulaca-oleracea-extract-in-alloxan-induced-diabetic-rats
#19
Basma K Ramadan, Mona F Schaalan, Amina M Tolba
BACKGROUND: Diabetes is a major public health concern. In spite of continuous new drug development to treat diabetes, herbal remedies remain a potential adjunct therapy to maintain better glycemic control while also imparting few side-effects. Portulaca oleracea has been traditionally used to manage several diseases due to the anti-oxidant and anti-atherogenic effects it imparts. To better understand the mechanisms associated with potential protective effect of P. oleracea extract against diabetes, alloxan-induced diabetic rats were used in this study...
January 11, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28072777/pancreatic-islets-find-a-new-transplant-home-in-the-omentum
#20
Charles Schmidt
No abstract text is available yet for this article.
January 10, 2017: Nature Biotechnology
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