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https://www.readbyqxmd.com/read/28107503/osteopontin-affects-insulin-vesicle-localization-and-ca2-homeostasis-in-pancreatic-beta-cells-from-female-mice
#1
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/28101643/polymorphisms-in-genes-encoding-mir-155-and-mir-146a-are-associated-with-protection-to-type-1-diabetes-mellitus
#2
Taís S Assmann, Guilherme C K Duarte, Letícia A Brondani, Pedro H O de Freitas, Égina M Martins, Luís H Canani, Daisy Crispim
AIMS: Type 1 diabetes mellitus (T1DM) is characterized by severe autoimmune destruction of pancreatic beta-cells. The triggering of autoimmunity against beta-cells is probably caused by a combination of environmental and genetic risk factors. Even though much is known about the genetic of T1DM, more information is needed to completely unravel this tangled disease. MicroRNAs (miRNAs) are a class of small noncoding RNAs molecules that negatively regulate gene expression by inducing target mRNA cleavage or by inhibiting protein translation...
January 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28095040/consensus-statement-by-the-american-association-of-clinical-endocrinologists-and-american-college-of-endocrinology-on-the-comprehensive-type-2-diabetes-management-algorithm-2017-executive-summary
#3
Alan J Garber, Martin J Abrahamson, Joshua I Barzilay, Lawrence Blonde, Zachary T Bloomgarden, Michael A Bush, Samuel Dagogo-Jack, Ralph A DeFronzo, Daniel Einhorn, Vivian A Fonseca, Jeffrey R Garber, W Timothy Garvey, George Grunberger, Yehuda Handelsman, Irl B Hirsch, Paul S Jellinger, Janet B McGill, Jeffrey I Mechanick, Paul D Rosenblit, Guillermo E Umpierrez
EXECUTIVE SUMMARY This algorithm for the comprehensive management of persons with type 2 diabetes (T2D) was developed to provide clinicians with a practical guide that considers the whole patient, their spectrum of risks and complications, and evidence-based approaches to treatment. It is now clear that the progressive pancreatic beta-cell defect that drives the deterioration of metabolic control over time begins early and may be present before the diagnosis of diabetes (1). In addition to advocating glycemic control to reduce microvascular complications, this document highlights obesity and prediabetes as underlying risk factors for the development of T2D and associated macrovascular complications...
January 17, 2017: Endocrine Practice
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
#4
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/28093996/challenges-related-to-glycemic-control-in-type-2-diabetes-mellitus-patients
#5
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Mohammad Amjad Kamal
Diabetes mellitus (DM) is a chronic disease with long-term complications. Glycemic control is an important part in management of DM. The first line in treatment of type 2 DM (T2DM) is diet and life style change. Metformin is the first choice of medication in T2DM patients. Sulfonylureas have high risk of hypoglycemia. Glinides are associated with lower risk of hypoglycemia in comparison to sulfonylureas. Also α-glucosidase inhibitors decrease the polysacarides digestion in small intestine and less effective in comparison to metformin and sulfonylureas in lowering hemoglobin A1c (HbA1c)...
January 15, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28088520/palmitic-acid-increases-invasiveness-of-pancreatic-cancer-cells-aspc-1-through-tlr4-ros-nf-%C3%AE%C2%BAb-mmp-9-signaling-pathway
#6
Makena J Binker-Cosen, Daniel Richards, Brenda Oliver, Herbert Y Gaisano, Marcelo G Binker, Laura I Cosen-Binker
Pancreatic cancer (PC) is an aggressive malady with proclivity for early metastasis. Overexpression of toll-like receptor 4 (TLR4) in pancreatic ductal adenocarcinoma, the most common type of pancreatic malignancy, correlates to tumor size, lymph node involvement, venous invasion and pathological stage. Lipopolysaccharides (LPS) are natural TLR4 ligands that have been shown to increase the invasive ability of PC cells. However, rapid inactivation of circulating LPS and low systemic absorption of inhaled LPS from the bronchoalveolar compartment make other agonists such as saturated fatty acids more suitable to be considered for TLR4-related cell invasiveness...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28086938/alpha-enolase-eno1-controls-alpha-v-beta-3-integrin-expression-and-regulates-pancreatic-cancer-adhesion-invasion-and-metastasis
#7
Moitza Principe, Simone Borgoni, Mariafrancesca Cascione, Michelle Samuel Chattaragada, Sammy Ferri-Borgogno, Michela Capello, Sara Bulfamante, Jennifer Chapelle, Francesca Di Modugno, Paola Defilippi, Paola Nisticò, Paola Cappello, Chiara Riganti, Stefano Leporatti, Francesco Novelli
BACKGROUND: We have previously shown that in pancreatic ductal adenocarcinoma (PDA) cells, the glycolytic enzyme alpha-enolase (ENO1) also acts as a plasminogen receptor and promotes invasion and metastasis formation. Moreover, ENO1 silencing in PDA cells induces oxidative stress, senescence and profoundly modifies PDA cell metabolism. Although anti-ENO1 antibody inhibits PDA cell migration and invasion, little is known about the role of ENO1 in regulating cell-cell and cell-matrix contacts...
January 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28079868/cdc123-camk1d-gene-rs12779790-polymorphism-and-rs10811661-polymorphism-upstream-of-the-cdkn2a-2b-gene-in-women-with-gestational-diabetes
#8
M Tarnowski, D Malinowski, K Safranow, V Dziedziejko, A Pawlik
OBJECTIVE: Gestational diabetes mellitus (GDM) is carbohydrate intolerance occurring in pregnant women. CDC123/CAMK1D and CDKN2A/2B are associated with increased risk of type 2 diabetes and may affect pancreatic beta cell function. The aim of this study was to examine the association between CDKN2A/2B rs10811661 and CDC123/CAMK1D rs12779790 gene polymorphisms and GDM. STUDY DESIGN: This study included 411 pregnant women. The diagnosis of GDM was based on the International Association of Diabetes and Pregnancy Study Groups criteria...
January 12, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28078386/early-differences-in-islets-from-prediabetic-nod-mice-combined-microarray-and-proteomic-analysis
#9
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
#10
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
#11
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/28076318/beta-cell-function-and-clinical-course-in-three-siblings-with-thiamine-responsive-megaloblastic-anemia-trma-treated-with-thiamine-supplementation
#12
Kathryn Potter, John Wu, Julie Lauzon, Josephine Ho
Three siblings with thiamine-responsive megaloblastic anemia (TRMA) with a homozygous c.454delGGCATinsAT mutation in SLC19A2 are described. The index case presented at 14 months' old with severe non-ketotic hyperglycemia, dehydration, seizures and sinovenous thrombosis. She was started on insulin and developed sensorineural hearing loss around 2 years old. Two siblings were found to have the same mutation and were started on thiamine. One sibling developed transient hyperglycemia after several years of thiamine supplementation of 12 mg/kg that resolved with an increased thiamine dose (23 mg/kg)...
January 11, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28069397/influence-of-neuropeptide-y-and-pancreatic-polypeptide-on-islet-function-and-beta-cell-survival
#13
Dawood Khan, Srividya Vasu, R Charlotte Moffett, Nigel Irwin, Peter R Flatt
BACKGROUND: In the present study we assessed the impact of neuropeptide Y receptor (NPYR) modulators, neuropeptide Y (NPY) and pancreatic polypeptide (PP), on islet function and beta-cell survival. METHODS: The effects of NPY and PP on beta-cell function were examined in BRIN BD11 and 1.1B4 beta-cells, as well as isolated mouse islets. Involvement of both peptides in pancreatic islet adaptations to streptozotocin and hydrocortisone, as well as effects on beta-cell proliferation and apoptosis was also evaluated...
January 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28067794/the-tgf-%C3%AE-smad4-signaling-pathway-in-pancreatic-carcinogenesis-and-its-clinical-significance
#14
REVIEW
Sunjida Ahmed, Azore-Dee Bradshaw, Shweta Gera, M Zahidunnabi Dewan, Ruliang Xu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human cancers due to its complicated genomic instability. PDAC frequently presents at an advanced stage with extensive metastasis, which portends a poor prognosis. The known risk factors associated with PDAC include advanced age, smoking, long-standing chronic pancreatitis, obesity, and diabetes. Its association with genomic and somatic mutations is the most important factor for its aggressiveness. The most common gene mutations associated with PDAC include KRas2, p16, TP53, and Smad4...
January 5, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28065853/sitagliptin-inhibit-human-lymphocytes-proliferation-and-th1-th17-differentiation-in-vitro
#15
Marcelo Maia Pinheiro, Caroline Lais Stoppa, Claudete Justina Valduga, Cristina Eunice Okuyama, Renata Gorjão, Regina Mara Silva Pereira, Susana Nogueira Diniz
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin...
January 5, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28062922/interferon-%C3%AE-mediates-human-beta-cell-hla-class-i-overexpression-endoplasmic-reticulum-stress-and-apoptosis-three-hallmarks-of-early-human-type-1-diabetes
#16
Laura Marroqui, Reinaldo S Dos Santos, Anne Op de Beeck, Alexandra Coomans de Brachène, Lorella Marselli, Piero Marchetti, Decio L Eizirik
AIMS/HYPOTHESIS: Three hallmarks of the pancreatic islets in early human type 1 diabetes are overexpression of HLA class I, endoplasmic reticulum (ER) stress and beta cell apoptosis. The mediators of these phenomena remain to be defined. The type I interferon IFNα is expressed in human islets from type 1 diabetes patients and mediates HLA class I overexpression. We presently evaluated the mechanisms involved in IFNα-induced HLA class I expression in human beta cells and determined whether this cytokine contributes to ER stress and apoptosis...
January 6, 2017: Diabetologia
https://www.readbyqxmd.com/read/28039581/microrna-expression-profiles-of-human-ipscs-differentiation-into-insulin-producing-cells
#17
Guido Sebastiani, Marco Valentini, Giuseppina Emanuela Grieco, Giuliana Ventriglia, Laura Nigi, Francesca Mancarella, Silvia Pellegrini, Gianvito Martino, Valeria Sordi, Lorenzo Piemonti, Francesco Dotta
AIMS: MicroRNAs are a class of small noncoding RNAs, which control gene expression by inhibition of mRNA translation. MicroRNAs are involved in the control of biological processes including cell differentiation. Here, we aim at characterizing microRNA expression profiles during differentiation of human induced pluripotent stem cells (hiPSCs) into insulin-producing cells. METHODS: We differentiated hiPSCs toward endocrine pancreatic lineage following a 18-day protocol...
December 30, 2016: Acta Diabetologica
https://www.readbyqxmd.com/read/28039012/personalized-glucose-insulin-model-based-on-signal-analysis
#18
Simon L Goede, Bastiaan E de Galan, Melvin Khee Shing Leow
Glucose plasma measurements for diabetes patients are generally presented as a glucose concentration-time profile with 15-60min time scale intervals. This limited resolution obscures detailed dynamic events of glucose appearance and metabolism. Measurement intervals of 15minutes or more could contribute to imperfections in present diabetes treatment. High resolution data from mixed meal tolerance tests (MMTT) for 24 type 1 and type 2 diabetes patients were used in our present modelling. We introduce a model based on the physiological properties of transport, storage and utilization...
December 27, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28032446/magnetic-resonance-imaging-of-intra-pancreatic-ductal-nanoparticle-delivery-to-islet-cells
#19
Ping Wang, Alana Ross, Byunghee Yoo, Jingsheng Yang, Christian Farrar, Chongzhao Ran, Pamela Pantazopoulos, Zdravka Medarova, Anna Moore
The absence of reliable drug delivery systems to pancreatic beta-cells hampers efficient treatment of type 1 diabetes. Nanoparticle delivery systems equipped with imaging capabilities could enable selective delivery to pancreatic islet cells. Biodistribution of nanoparticles is defined by several factors including the mode of administration, which determines accumulation in various organs. In this study we tested whether intra-pancreatic ductal injection of magnetic nanoparticles (MN) would result in efficient cellular uptake by pancreatic islet cells...
December 29, 2016: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28028829/localization-of-nucleic-acid-sensing-toll-like-receptors-in-human-and-mouse-pancreas
#20
Olli Helminen, Heikki Huhta, Joonas H Kauppila, Petri P Lehenkari, Juha Saarnio, Tuomo J Karttunen
Nucleic acid-sensing toll-like receptors (TLRs) (3, 7, 8, 9) have a role both in antiviral innate immunity and in autoimmune disorders. We assessed the expression of TLR3, 7, 8 and 9 in human and mouse pancreas focusing on the subpopulations of cells in the Langerhans islets. We studied eight human samples with normal pancreatic islets and two samples from patients with type 1 diabetes. Additionally, 10 CD-1 mouse pancreases were analysed. Immunohistochemical double-stainings for the TLRs and insulin, glucagon or somatostatin, respectively, were performed along with appropriate controls...
December 28, 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
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