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https://www.readbyqxmd.com/read/29130298/role-of-micrornas-mirnas-in-pathophysiology-of-diabetes-mellitus
#1
Juhi Tiwari, Gaurav Gupta, Terezinha de Jesus Andreoli Pinto, Rahul Sharma, Kavita Pabreja, Yogesh Matta, Neha Arora, Anurag Mishra, Rakesh Sharma, Kamal Dua
Diabetes Mellitus is becoming the critical problem among the entire world and it is difficult to understand the molecular mechanism representing the concept of diabetic pathology. Recently the knowledge of the involvement of genetics in type 2 diabetes mellitus (T2DM) susceptibility has sketched a great concentration towards the transcriptional activity of ß cells within the pancreas. This disease becomes the leading cause of death so it is necessary to study the molecular pathogenesis, phenotypes, and characteristics to design the therapeutic parameters...
November 10, 2017: Panminerva Medica
https://www.readbyqxmd.com/read/29128936/hospital-time-prior-to-death-and-pancreas-histopathology-implications-for-future-studies
#2
Irina Kusmartseva, Maria Beery, Tiffany Philips, Stephen Selman, Priyanka Jadhav, Clive Wasserfall, Axel Muller, Alberto Pugliese, Jeffrey A Longmate, Desmond A Schatz, Mark A Atkinson, John S Kaddis
AIMS/HYPOTHESIS: Diabetes research studies routinely rely upon the use of tissue samples from human organ donors. It remains unclear whether the length of hospital stay prior to organ donation affects the presence of cells infiltrating the pancreas or the frequency of replicating beta cells. METHODS: To address this, 39 organ donors without diabetes were matched for age, sex, BMI and ethnicity in groups of three. Within each group, donors varied by length of hospital stay immediately prior to organ donation (<3 days, 3 to <6 days, or ≥6 days)...
November 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/29123178/a-nanobody-based-tracer-targeting-dpp6-for-non-invasive-imaging-of-human-pancreatic-endocrine-cells
#3
Alexander Balhuizen, Sam Massa, Iris Mathijs, Jean-Valery Turatsinze, Jens De Vos, Stéphane Demine, Catarina Xavier, Olatz Villate, Isabelle Millard, Dominique Egrise, Carmen Capito, Raphaël Scharfmann, Pieter In't Veld, Piero Marchetti, Serge Muyldermans, Serge Goldman, Tony Lahoutte, Luc Bouwens, Decio L Eizirik, Nick Devoogdt
There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29119245/development-and-characterisation-of-a-novel-glucagon-like-peptide-1-receptor-antibody
#4
Emma K Biggs, Lihuan Liang, Jacqueline Naylor, Shimona Madalli, Rachel Collier, Matthew P Coghlan, David J Baker, David C Hornigold, Peter Ravn, Frank Reimann, Fiona M Gribble
AIMS/HYPOTHESIS: Glucagon like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion by binding to GLP-1 receptors (GLP1Rs) on pancreatic beta cells. GLP-1 mimetics are used in the clinic for the treatment of type 2 diabetes, but despite their therapeutic success, several clinical effects of GLP-1 remain unexplained at a mechanistic level, particularly in extrapancreatic tissues. The aim of this study was to generate and characterise a monoclonal antagonistic antibody for the GLP1R for use in vivo...
November 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/29107594/genes-associated-with-pancreas-development-and-function-maintain-open-chromatin-in-ipscs-generated-from-human-pancreatic-beta-cells
#5
Matthias Thurner, Liraz Shenhav, Agata Wesolowska-Andersen, Amanda J Bennett, Amy Barrett, Anna L Gloyn, Mark I McCarthy, Nicola L Beer, Shimon Efrat
Current in vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced pluripotent stem cells (iPSCs) derived from pancreatic beta cells (BiPSCs) preferentially differentiate toward endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identified ∼8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (false discovery rate [FDR] < 0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29096722/pdx1-neurogenin-3-and-mafa-critical-transcription-regulators-for-beta-cell-development-and-regeneration
#6
REVIEW
Yaxi Zhu, Qian Liu, Zhiguang Zhou, Yasuhiro Ikeda
Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells...
November 2, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29080463/ameliorative-effects-of-bee-pollen-and-date-palm-pollen-on-the-glycemic-state-and-male-sexual-dysfunctions-in-streptozotocin-induced-diabetic-wistar-rats
#7
Nema A Mohamed, Osama M Ahmed, Walaa G Hozayen, Marium A Ahmed
This study aimed to assess the effects of bee pollen (BP) and/or date palm pollen (DPP) suspensions on the glycemic state, testicular dysfunctions, oxidative stress and antioxidant defense system in streptozotocin (STZ)-induced diabetic male Wistar rats. Diabetes mellitus was induced by single intraperitoneal injection of STZ to overnight-fasted rats at dose of 40mg/kg body weight. After 1 week of STZ injection, diabetic rats were treated with BP and/or DPP suspensions at dose levels of 100mg/kg body weight/day for 4 weeks...
October 25, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29079704/mitochondrial-protein-ucp2-controls-pancreas-development
#8
Benjamin Broche, Selma Ben Fradj, Esther Aguilar, Tiphaine Sancerni, Matthieu Bénard, Fatna Makaci, Claire Berthault, Raphaël Scharfmann, Marie-Clotilde Alves-Guerra, Bertrand Duvillié
The mitochondrial carrier UCP2 belongs to the family of the uncoupling proteins. Despite its name, it is now accepted that UCP2 is rather a metabolite transporter than an uncoupling protein. UCP2 can regulate oxidative stress and/or energetic metabolism. In rodents, UCP2 is involved in the control of alpha- and beta-cell mass as well as insulin- and glucagon-secretion. Our aim was to determine whether the effects of UCP2 observed on beta-cell mass have an embryonic origin. Thus, we used Ucp2 knock-out mice...
October 27, 2017: Diabetes
https://www.readbyqxmd.com/read/29064047/pancreatic-imaging-using-an-antibody-fragment-targeting-the-zinc-transporter-type-8-a-direct-comparison-with-radio-iodinated-exendin-4
#9
Olof Eriksson, Olle Korsgren, Ram Kumar Selvaraju, Marjorie Mollaret, Yann de Boysson, Fabrice Chimienti, Mohamed Altai
AIM: The zinc transporter 8 (ZnT8) has been suggested as a suitable target for non-invasive visualization of the functional pancreatic beta cell mass, due to both its pancreatic beta cell restricted expression and tight involvement in insulin secretion. METHODS: In order to examine the potential of ZnT8 as a surrogate target for beta cell mass, we performed mRNA transcription analysis in pancreatic compartments. A novel ZnT8 targeting antibody fragment Ab31 was radiolabeled with iodine-125, and evaluated by in vitro autoradiography in insulinoma and pancreas as well as by in vivo biodistribution...
October 24, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/29057588/gub06-046-a-novel-secretin-glucagon-like-peptide-1-co-agonist-decreases-food-intake-improves-glycemic-control-and-preserves-beta-cell-mass-in-diabetic-mice
#10
Søren B van Witteloostuijn, Louise S Dalbøge, Gitte Hansen, Søren Roi Midtgaard, Grethe Vestergaard Jensen, Knud J Jensen, Niels Vrang, Jacob Jelsing, Søren L Pedersen
Bariatric surgery is currently the most effective treatment of obesity, which has spurred an interest in developing pharmaceutical mimetics. It is thought that the marked body weight-lowering effects of bariatric surgery involve stimulated secretion of appetite-regulating gut hormones, including glucagon-like peptide 1. We here report that intestinal expression of secretin is markedly upregulated in a rat model of Roux-en-Y gastric bypass, suggesting an additional role of secretin in the beneficial metabolic effects of Roux-en-Y gastric bypass...
October 23, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29057252/glis1-3-emerging-roles-in-reprogramming-stem-and-progenitor-cell-differentiation-and-maintenance
#11
REVIEW
David W Scoville, Hong Soon Kang, Anton M Jetten
Recent studies have provided evidence for a regulatory role of GLI-similar (GLIS) transcription factors in reprogramming, maintenance and differentiation of several stem and progenitor cell populations. GLIS1, in conjunction with several other reprogramming factors, was shown to markedly increase the efficiency of generating induced pluripotent stem cells (iPSC) from somatic cells. GLIS2 has been reported to contribute to the maintenance of the pluripotent state in hPSCs. In addition, GLIS2 has a function in regulating self-renewal of hematopoietic progenitors and megakaryocytic differentiation...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/29053717/gpr40-partial-agonists-and-agopams-differentiating-effects-on-glucose-and-hormonal-secretions-in-the-rodent
#12
Michele J Pachanski, Melissa E Kirkland, Daniel T Kosinski, Joel Mane, Boonlert Cheewatrakoolpong, Jiyan Xue, Daphne Szeto, Gail Forrest, Corin Miller, Michelle Bunzel, Christopher W Plummer, Harry R Chobanian, Michael W Miller, Sarah Souza, Brande S Thomas-Fowlkes, Aimie M Ogawa, Adam B Weinglass, Jerry Di Salvo, Xiaoyan Li, Yue Feng, Daniel A Tatosian, Andrew D Howard, Steven L Colletti, Maria E Trujillo
GPR40 agonists are effective antidiabetic agents believed to lower glucose through direct effects on the beta cell to increase glucose stimulated insulin secretion. However, not all GPR40 agonists are the same. Partial agonists lower glucose through direct effects on the pancreas, whereas GPR40 AgoPAMs may incorporate additional therapeutic effects through increases in insulinotrophic incretins secreted by the gut. Here we describe how GPR40 AgoPAMs stimulate both insulin and incretin secretion in vivo over time in diabetic GK rats...
2017: PloS One
https://www.readbyqxmd.com/read/29051963/applications-of-particulate-oxygen-generating-substances-pogs-in-the-bioartificial-pancreas
#13
John P McQuilling, Sivanandane Sittadjody, Samuel Pendergraft, Alan C Farney, Emmanuel C Opara
Type-1 Diabetes (T1D) is a devastating autoimmune disorder which results in the destruction of beta cells within the pancreas. A promising treatment strategy for T1D is the replacement of the lost beta cell mass through implantation of immune-isolated microencapsulated islets referred to as the bioartificial pancreas. The goal of this approach is to restore blood glucose regulation and prevent the long-term comorbidities of T1D without the need for immunosuppressants. A major requirement in the quest to achieve this goal is to address the oxygen needs of islet cells...
October 20, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29044779/exocrine-pancreas-function-decreases-during-the-progression-of-the-beta-cell-damaging-process-in-young-prediabetic-children
#14
Anita Kondrashova, Noora Nurminen, Jussi Lehtonen, Marja Hyöty, Jorma Toppari, Jorma Ilonen, Riitta Veijola, Mikael Knip, Heikki Hyöty
OBJECTIVE: The function of the exocrine pancreas is decreased in patients with type 1 diabetes but it is not known when this defect develops. The current study set out to determine whether the reduced exocrine function becomes manifest after the initiation of islet autoimmunity. METHODS: The study was nested in the prospective Type 1 Diabetes Prediction and Prevention study where children with human leukocyte antigen (HLA)-conferred susceptibility are observed from birth...
October 17, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/29023012/levels-of-blood-glucose-and-insulin-expression-of-beta-cells-in-streptozotocin-induced-diabetic-rats-treated-with-ethanolic-extract-of-artocarpus-altilis-leaves-and-gaba
#15
Meti Indrowati, Rarastoeti Pratiwi, Rumiyati, Pudji Astuti
BACKGROUND AND OBJECTIVE: Information about the Artocarpus altilis leaf as an antidiabetic associated with the active compounds Gamma Amino Butyric Acid (GABA) is still limited. This study was conducted to determine the effects of ethanolic extract of A. altilis leaves decoction and GABA on blood glucose levels and insulin expression of beta-cells in streptozotocin-induced diabetic rats. MATERIAL AND METHODS: This study was done by using completely randomized design and male Sprague Dewley rats...
2017: Pakistan Journal of Biological Sciences: PJBS
https://www.readbyqxmd.com/read/28993759/the-four-way-stop-sign-viruses-12-lipoxygenase-islets-and-natural-killer-cells-in-type-1-diabetes-progression
#16
Michele L Semeraro, Lindsey M Glenn, Margaret A Morris
Natural killer (NK) cells represent an important effector arm against viral infection, and mounting evidence suggests that viral infection plays a role in the development of type 1 diabetes (T1D) in at least a portion of patients. NK cells recognize their target cells through a delicate balance of inhibitory and stimulatory receptors on their surface. If unbalanced, NK cells have great potential to wreak havoc in the pancreas due to the beta cell expression of the as-yet-defined NKp46 ligand through interactions with the activating NKp46 receptor found on the surface of most NK cells...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28986402/microrna-expression-profiles-and-type-1-diabetes-mellitus-systematic-review-and-bioinformatic-analysis
#17
Taís S Assmann, Mariana Recamonde-Mendoza, Bianca M De Souza, Daisy Crispim
Growing evidence indicates that microRNAs (miRNAs) have a key role in processes involved in type 1 diabetes mellitus (T1DM) pathogenesis, including immune system functions and beta-cell metabolism and death. Although dysregulated miRNA profiles have been identified in T1DM patients, results are inconclusive; with only few miRNAs being consistently dysregulated among studies. Thus, we performed a systematic review of the literature on the subject, followed by bioinformatic analysis, to point out which miRNAs are dysregulated in T1DM-related tissues and in which pathways they act...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28984038/beta-cell-replacement-strategies-for-diabetes
#18
Timothy J Kieffer, Knut Woltjen, Kenji Osafune, Daisuke Yabe, Nobuya Inagaki
Diabetes is characterized by elevated levels of blood glucose as a result of insufficient production of insulin from loss or dysfunction of pancreatic islet beta cells. Here we review several approaches to replace beta cells that were recently discussed at a symposium held in Kyoto, Japan. Transplant of donor human islets can effectively treat diabetes and eliminate the need for insulin injections, supporting research aimed at identifying abundant supplies of cells. Studies demonstrating the feasibility of producing mouse islets in rats support the concept of generating pigs with human pancreas that can serve as donors of human islets, although scientific and ethical challenges remain...
October 6, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28977592/cftr-influences-beta-cell-function-and-insulin-secretion-through-non-cell-autonomous-exocrine-derived-factors
#19
Xingshen Sun, Yaling Yi, Weiliang Xie, Bo Liang, Michael C Winter, Nan He, Xiaoming Liu, Meihui Luo, Yu Yang, Katie Larson Ode, Aliye Uc, Andrew W Norris, John F Engelhardt
Although β-cell dysfunction in cystic fibrosis (CF) leads to diabetes, the mechanism by which the cystic fibrosis transmembrane conductance regulator (CFTR) channel influences islet insulin secretion remains debated. We investigated the CFTR-dependent islet-autonomous mechanisms affecting insulin secretion by using islets isolated from CFTR knockout ferrets. Total insulin content was lower in CF as compared with wild-type (WT) islets. Furthermore, glucose-stimulated insulin secretion (GSIS) was impaired in perifused neonatal CF islets, with reduced first, second, and amplifying phase secretion...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28974943/fresh-ideas-foundational-experiments-fife-immunology-and-diabetes-2016-fife-symposium
#20
Isobel C Mouat, Zachary J Morse, Virginie S E Jean-Baptiste, Jessica R Allanach, Marc S Horwitz
The first Fresh Ideas, Foundational Experiments (FIFE): Immunology and Diabetes symposia workshop took place in 2016 and exemplified the active interest of a number of several investigators interested the global rise in the incidence of type 1 diabetes (T1D). This increase does not correlate with genetic drift and indicates that environmental exposures are playing an increasingly significant role. Despite major biomedical and technological advances in diagnosis and treatment, treatments are frequently insufficient as they do not inhibit the progression of the underlying autoimmune response and often fail to prevent life-threatening complications...
2017: Frontiers in Endocrinology
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