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https://www.readbyqxmd.com/read/28646700/increased-serum-mir-7-is-a-promising-biomarker-for-type-2-diabetes-mellitus-and-its-microvascular-complications
#1
Shujun Wan, Jun Wang, Jing Wang, Jia Wu, Jiaxi Song, Chen-Yu Zhang, Chunni Zhang, Cheng Wang, Jun-Jun Wang
AIMS: To investigate the alteration pattern and physiologic state of islet-specific miR-7 in the serum of patients with type 2 diabetes mellitus (T2DM) and T2DM-associated microvascular complications (T2DMC) and to evaluate its clinical significance. METHODS: The levels of serum miR-7 were firstly examined and compared in 76 T2DM patients, 76 T2DMC patients and 74 age-gender matched controls using RT-qPCR. Subsequently, the physiologic state of serum miR-7 was characterized by determining its concentrations in isolated exosomes and corresponding exosome-free samples from the same three cohorts' samples...
June 11, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28646072/genetic-and-environmental-interactions-modify-the-risk-of-diabetes-related-autoimmunity-by-6-years-of-age-the-teddy-study
#2
Jeffrey P Krischer, Kristian F Lynch, Åke Lernmark, William A Hagopian, Marian J Rewers, Jin-Xiong She, Jorma Toppari, Anette-G Ziegler, Beena Akolkar
OBJECTIVE: We tested the associations between genetic background and selected environmental exposures with respect to islet autoantibodies and type 1 diabetes. RESEARCH DESIGN AND METHODS: Infants with HLA-DR high-risk genotypes were prospectively followed for diabetes-related autoantibodies. SNPs came from the Illumina ImmunoChip and environmental exposure data were by parental report. Children were followed to age 6 years. RESULTS: Insulin autoantibodies occurred earlier than GAD antibody (GADA) and then declined, while GADA incidence rose and remained constant (significant in HLA-DR4 but not in the DR3/3 children)...
June 23, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28646042/on-the-role-il-4-il-13-heteroreceptor-plays-in-regulation-of-type-1-diabetes
#3
Tobechukwu K Ukah, Alexis N Cattin-Roy, Weirong Chen, Mindy M Miller, Subhasis Barik, Habib Zaghouani
Type 1 diabetes (T1D) manifests when the insulin-producing pancreatic β cells are destroyed as a consequence of an inflammatory process initiated by lymphocytes of the immune system. The NOD mouse develops T1D spontaneously and serves as an animal model for human T1D. The IL-4Rα/IL-13Rα1 heteroreceptor (HR) serves both IL-4 and IL-13 cytokines, which are believed to function as anti-inflammatory cytokines in T1D. However, whether the HR provides a responsive element to environmental (i.e., physiologic) IL-4/IL-13 in the regulation of peripheral tolerance and the development of T1D has yet to be defined...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28643938/oral-application-of-a-periodontal-pathogen-impacts-serpine1-expression-and-pancreatic-islet-architecture-in-prediabetes
#4
V Ilievski, U G Bhat, S Suleiman-Ata, B A Bauer, P T Toth, S T Olson, T G Unterman, K Watanabe
BACKGROUND AND OBJECTIVES: Epidemiological studies suggest a close association between periodontitis and prediabetes/insulin resistance (IR) but whether periodontitis causes prediabetes in humans is not known. Using various animal models, we have recently established that periodontitis can be an initiator of prediabetes, which is characterized by glucose intolerance, hyperinsulinemia and IR. In addition, our in vitro studies indicated that Porphyromonas gingivalis (Pg) induced insulin secretion in MIN6 β cells and this induction was in part SerpinE1 (plasminogen activator inhibitor 1, PAI1) dependent...
June 23, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28643455/pathways-governing-development-of-stem-cell-derived-pancreatic-%C3%AE-cells-lessons-from-embryogenesis
#5
Sara Al-Khawaga, Bushra Memon, Alexandra E Butler, Shahrad Taheri, Abdul B Abou-Samra, Essam M Abdelalim
The loss of functional β cells leads to development of diabetes. Several studies have shown that β cells are specified through several stages of progenitors during pancreas development, each stage defined by the expression of specific transcription factors (TFs). Understanding signalling pathways that control the differentiation and specification processes during embryogenesis will facilitate efforts to obtain functional β cells in vitro. Our current knowledge of the mechanisms involved in pancreatic β cell development and survival under normal or diabetic conditions has come largely from animal studies...
June 22, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28640379/comparative-and-correlative-assessments-of-cytokine-complement-and-antibody-patterns-in-pediatric-type-1-diabetes
#6
M Abdel-Latif, A A Abdel-Moneim, M H El-Hefnawy, R G Khalil
One of the most widespread and effective environmental factors is the infection with enteroviruses (EVs) which accelerate β - cell destruction in type 1 diabetes (T1D). This study represented a comparison between diabetic EV(+) and EV- children as well as correlation analysis between autoantibodies, T1D markers, cytokines, complement activation products and anti- coxsackievirus (CV) IgG. EV RNA was detected in Egyptian children with T1D (26.2%) and healthy controls (0%). Detection of anti - CV IgG in T1D - EV(+) resulted in 64% positivity...
June 22, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28639386/development-of-immune-response-to-tissue-restricted-self-antigens-in-simultaneous-kidney-pancreas-transplant-recipients-with-acute-rejection
#7
Muthukumar Gunasekaran, Neeta Vachharajani, Joseph P Gaut, Thin Thin Maw, Rowena Delos Santos, Surendra Shenoy, William C Chapman, Jason Wellen, Thalachallour Mohanakumar
Simultaneous kidney-pancreas transplantation (SKP Tx) is a treatment for end-stage kidney disease secondary to diabetes mellitus. We investigated the role of immune responses to donor human leukocyte antigens (HLA) and tissue-restricted kidney and pancreas self-antigens (KSAgs and PSAgs, respectively) in SKP Tx recipients (SKP TxRs). Sera collected from 39 SKP TxRs were used to determine de novo Abs specific for KSAgs (collagen-IV, Col-IV; fibronectin, FN) and PSAgs (insulin, islet cells, glutamic acid decarboxylase, and pancreas-associated protein-1) by ELISA...
June 21, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28637827/islet-encapsulation-physiological-possibilities-and-limitations
#8
Olle Korsgren
A logical cure for type 1 diabetes (T1D) involves replacing the lost insulin-producing cells with new ones, preferably cells from a well-characterized and unlimited source of human insulin-producing cells. This straightforward and simple solution to provide a cure for T1D is immensely attractive but entails at least two inherent and thus far unresolved hurdles: 1) provision of an unlimited source of functional human insulin-producing cells and 2) prevention of rejection without the side effects of systemic immunosuppression...
July 2017: Diabetes
https://www.readbyqxmd.com/read/28637794/a-trpv1-to-secretagogin-regulatory-axis-controls-pancreatic-%C3%AE-cell-survival-by-modulating-protein-turnover
#9
Katarzyna Malenczyk, Fatima Girach, Edit Szodorai, Petter Storm, Åsa Segerstolpe, Giuseppe Tortoriello, Robert Schnell, Jan Mulder, Roman A Romanov, Erzsébet Borók, Fabiana Piscitelli, Vincenzo Di Marzo, Gábor Szabó, Rickard Sandberg, Stefan Kubicek, Gert Lubec, Tomas Hökfelt, Ludwig Wagner, Leif Groop, Tibor Harkany
Ca(2+)-sensor proteins are generally implicated in insulin release through SNARE interactions. Here, secretagogin, whose expression in human pancreatic islets correlates with their insulin content and the incidence of type 2 diabetes, is shown to orchestrate an unexpectedly distinct mechanism. Single-cell RNA-seq reveals retained expression of the TRP family members in β-cells from diabetic donors. Amongst these, pharmacological probing identifies Ca(2+)-permeable transient receptor potential vanilloid type 1 channels (TRPV1) as potent inducers of secretagogin expression through recruitment of Sp1 transcription factors...
June 21, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28636327/maldi-ms-guided-liquid-microjunction-extraction-for-ce-esi-ms-analysis-of-single-pancreatic-islet-cells
#10
Troy J Comi, Monika A Makurath, Marina C Philip, Stanislav S Rubakhin, Jonathan V Sweedler
The ability to characterize chemical heterogeneity in biological structures is essential to understanding cellular level function in both healthy and diseased states, but these variations remain difficult to assess using a single analytical technique. While mass spectrometry (MS) provides sufficient sensitivity to measure many analytes from volume-limited samples, each type of mass spectrometric analysis uncovers only a portion of the complete chemical profile of a single cell. Matrix-assisted laser desorp-tion/ionization (MALDI) MS and capillary electrophoresis electrospray ionization (CE-ESI)-MS are complementary analytical platforms frequently utilized for single cell analysis...
June 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28634815/autoimmune-diabetes-induced-by-pd-1-inhibitor-retrospective-analysis-and-pathogenesis-a-case-report-and-literature-review
#11
Marie-Léa Gauci, Pauline Laly, Tiphaine Vidal-Trecan, Barouyr Baroudjian, Jérémy Gottlieb, Nika Madjlessi-Ezra, Laetitia Da Meda, Isabelle Madelaine-Chambrin, Martine Bagot, Nicole Basset-Seguin, Cécile Pages, Samia Mourah, Philippe Boudou, Céleste Lebbé, Jean-François Gautier
Anti-PD-1 antibody treatment is approved in advanced melanoma and provides median overall survival over 24 months. The main treatment-related side effects are immune-related adverse events, which include rash, pruritus, vitiligo, thyroiditis, diarrhoea, hepatitis and pneumonitis. We report a case of autoimmune diabetes related to nivolumab treatment. A 73-year-old man was treated in second line with nivolumab at 3 mg/kg every two weeks for metastatic melanoma. At 6 weeks of treatment, he displayed diabetic ketoacidosis...
June 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28632821/encapsulated-islet-transplantation-where-do-we-stand
#12
Vijayaganapathy Vaithilingam, Sumeet Bal, Bernard E Tuch
Transplantation of pancreatic islets encapsulated within immuno-protective microcapsules is a strategy that has the potential to overcome graft rejection without the need for toxic immunosuppressive medication. However, despite promising preclinical studies, clinical trials using encapsulated islets have lacked long-term efficacy, and although generally considered clinically safe, have not been encouraging overall. One of the major factors limiting the long-term function of encapsulated islets is the host's immunological reaction to the transplanted graft which is often manifested as pericapsular fibrotic overgrowth (PFO)...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28632820/the-nexus-of-stem-cell-derived-beta-cells-and-genome-engineering
#13
Sara D Sackett, Aida Rodriguez, Jon S Odorico
Diabetes, type 1 and type 2 (T1D and T2D), are diseases of epidemic proportions, which are complicated and defined by genetics, epigenetics, environment, and lifestyle choices. Current therapies consist of whole pancreas or islet transplantation. However, these approaches require life-time immunosuppression, and are compounded by the paucity of available donors. Pluripotent stem cells have advanced research in the fields of stem cell biology, drug development, disease modeling, and regenerative medicine, and importantly allows for the interrogation of therapeutic interventions...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28632819/enzyme-development-for-human-islet-isolation-five-decades-of-progress-or-stagnation
#14
Daniel Brandhorst, Heide Brandhorst, Paul R V Johnson
In comparison to procedures used for the separation of individual cell types from other organs, the process of human pancreatic islet isolation aims to digest the pancreatic exocrine matrix completely without dispersing the individual cells within the endocrine cell cluster. This objective is unique within the field of tissue separation, and outlines the challenge of islet isolation to balance two opposing priorities. Although significant progress has been made in the characterization and production of enzyme blends for islet isolation, there are still numerous areas which require improvement...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28632818/benefits-of-islet-transplantation-as-an-alternative-to-pancreas-transplantation-retrospective-study-of-more-than-10-ten-years-of-experience-in-a-single-center
#15
Barbora Voglová, Martina Zahradnická, Peter Girman, Jan Kríž, Zuzana Berková, Tomáš Koblas, Ema Vávrová, Lenka Németová, Lucie Kosinová, David Habart, Eva Fábryová, Eva Dovolilová, Ivan Leontovyc, Tomáš Neškudla, Jan Peregrin, Jozef Kovác, Kvetoslav Lipár, Matej Kocík, Tomáš Marada, Jirí Svoboda, František Saudek
BACKGROUND: Pancreas transplantation (PTx) represents the method of choice in type 1 diabetic patients with conservatively intractable hypoglycemia unawareness syndrome. In 2005, the Institute for Clinical and Experimental Medicine (IKEM) launched a program to investigate the safety potential of islet transplantation (ITx) in comparison to PTx. AIM: This study aims to compare the results of PTx and ITx regarding severe hypoglycemia elimination, metabolic control, and complication rate...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28630926/vasculogenic-hydrogel-enhances-islet-survival-engraftment-and-function-in-leading-extrahepatic-sites
#16
Jessica D Weaver, Devon M Headen, Jahizreal Aquart, Christopher T Johnson, Lonnie D Shea, Haval Shirwan, Andrés J García
Islet transplantation is a promising alternative therapy for insulin-dependent patients, with the potential to eliminate life-threatening hypoglycemic episodes and secondary complications of long-term diabetes. However, widespread application of this therapy has been limited by inadequate graft function and longevity, in part due to the loss of up to 60% of the graft in the hostile intrahepatic transplant site. We report a proteolytically degradable synthetic hydrogel, functionalized with vasculogenic factors for localized delivery, engineered to deliver islet grafts to extrahepatic transplant sites via in situ gelation under physiological conditions...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28630491/chronic-high-fat-feeding-restricts-islet-mrna-translation-initiation-independently-of-er-stress-via-dna-damage-and-p53-activation
#17
Masayuki Hatanaka, Emily Anderson-Baucum, Alexander Lakhter, Tatsuyoshi Kono, Bernhard Maier, Sarah A Tersey, Yukio Tanizawa, Carmella Evans-Molina, Raghavendra G Mirmira, Emily K Sims
Under conditions of high fat diet (HFD) consumption, glucose dyshomeostasis develops when β-cells are unable to adapt to peripheral insulin demands. Few studies have interrogated the molecular mechanisms of β-cell dysfunction at the level of mRNA translation under such conditions. We sought to address this issue through polyribosome profile analysis of islets from mice fed 16-weeks of 42% HFD. HFD-islet analysis revealed clear trends toward global reductions in mRNA translation with a significant reduction in the polyribosome/monoribosome ratio for Pdx1 mRNA...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630088/the-islet-resident-macrophage-is-in-an-inflammatory-state-and-senses-microbial-products-in-blood
#18
Stephen T Ferris, Pavel N Zakharov, Xiaoxiao Wan, Boris Calderon, Maxim N Artyomov, Emil R Unanue, Javier A Carrero
We examined the transcriptional profiles of macrophages that reside in the islets of Langerhans of 3-wk-old non-obese diabetic (NOD), NOD.Rag1(-/-), and B6.g7 mice. Islet macrophages expressed an activation signature with high expression of Tnf, Il1b, and MHC-II at both the transcript and protein levels. These features are common with barrier macrophages of the lung and gastrointestinal tract. Moreover, injection of lipopolysaccharide induced rapid inflammatory gene expression, indicating that blood stimulants are accessible to the macrophages and that these macrophages can sense them...
June 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28628651/the-density-of-parasympathetic-axons-is-reduced-in-the-exocrine-pancreas-of-individuals-recently-diagnosed-with-type-1-diabetes
#19
Marcus Lundberg, Andreas Lindqvist, Nils Wierup, Lars Krogvold, Knut Dahl-Jørgensen, Oskar Skog
To elucidate the etiology of type 1 diabetes, the affected pancreas needs to be thoroughly characterized. Pancreatic innervation has been suggested to be involved in the pathology of the disease and a reduction of sympathetic innervation of the islets was recently reported. In the present study, we hypothesized that parasympathetic innervation would be altered in the type 1 diabetes pancreas. Human pancreatic specimens were obtained from a unique cohort of individuals with recent onset or long standing type 1 diabetes...
2017: PloS One
https://www.readbyqxmd.com/read/28627773/oleanolic-acid-derivative-dks26-exerts-antidiabetic-and-hepatoprotective-effects-in-diabetic-mice-and-promotes-glp-1-secretion-and-expression-in-intestinal-cells
#20
Fei-Fei Chen, Jian-Ta Wang, Li-Xia Zhang, Shu-Fang Xing, Yun-Xia Wang, Kai Wang, Shu-Li Deng, Ji-Quan Zhang, Lei Tang, Hao-Shu Wu
BACKGROUND AND PURPOSE: Glucagon-like peptide-1 (GLP-1) is an important target for diabetes therapy based on its key role in maintaining glucose and lipid homeostasis. This study was designed to investigate antidiabetic and hepatoprotective effects of novel oleanolic acid derivative DKS26 in diabetic mice and elucidate its underlying GLP-1 related antidiabetic mechanisms in vitro and in vivo. EXPERIMENTAL APPROACH: The therapeutic effects of DKS26 were inspected in streptozotocin (STZ)-induced and db/db diabetic mouse models including levels of plasma glucose, glycosylated serum protein (GSP), lipid profiles, insulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), oral glucose tolerance (OGT), pancreatic islets and hepatic histopathological morphology, liver lipid levels and expression of pro-inflammation cytokines...
June 19, 2017: British Journal of Pharmacology
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