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Beta cell mass

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https://www.readbyqxmd.com/read/29144809/preserved-proinsulin-secretion-in-long-standing-type-1-diabetes
#1
Devin W Steenkamp, Jose M Cacicedo, Ayse Sahin-Efe, Catherine Sullivan, Elliot Sternthal
OBJECTIVE: Recent literature, has reported preserved residual beta cell function, (c-peptide "microsecretion") in many individuals with long standing type 1 diabetes. However, the concentrations of detectable insulin/c-peptide in the serum are usually very low, and beta cell mass is typically negligible. Proinsulin is measurable in the early years after diagnosis, consistent with the presence of residual functioning beta cells. However, individuals are not expected to secrete significant amounts of proinsulin beyond the early years after diagnosis...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29144805/dpp4-inhibitor-sitagliptin-as-a-potential-treatment-option-in-metformin-intolerant-obese-women-with-polycystic-ovary-syndrome-a-pilot-randomized-study
#2
Simona Ferjan, Andrej Janez, Mojca Jensterle
OBJECTIVE: Metformin has an established role in the management of polycystic ovary syndrome (PCOS). Some patients cannot tolerate it due to associated gastrointestinal adverse events. The present study evaluated DPP4 inhibitor sitagliptin as a potential treatment option in metformin intolerant PCOS. DESIGN: We conducted a 12-week prospective randomized open-label study with 30 obese metformin intolerant women with PCOS (aged 35.0±7.2 years, BMI 36.9±5.5 kg/m(2))...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29142396/antioxidant-and-cholinesterase-inhibitory-activities-of-ethyl-acetate-extract-of-terminalia-chebula-cell-free-in-vitro-and-in-silico-studies
#3
Mohamed Asik Rajmohamed, Suganthy Natarajan, Premkumar Palanisamy, Akbarsha Mohammad Abdulkader, Archunan Govindaraju
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by memory loss and impaired cognitive function. Cholinergic enzyme deficiency and oxidative stress are the two major factors implicated in the pathogenesis of AD. The symptomatic treatment, as of now, is the use of cholinesterase inhibitors toward cholinergic "downturn." Therefore, there is a search for compounds that will be useful in focused therapies. There has been suggestion that Terminalia chebula fruit would be a potential source...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29133594/competitive-kinase-enrichment-proteomics-reveals-that-abemaciclib-inhibits-gsk3%C3%AE-and-activates-wnt-signaling
#4
Emily M Cousins, Dennis Goldfarb, Feng Yan, Jose Roques, David B Darr, Gary L Johnson, Michael B Major
The cellular and organismal phenotypic response to a small-molecule kinase inhibitor is defined collectively by the inhibitor's targets and their functions. The selectivity of small-molecule kinase inhibitors is commonly determined in vitro, using purified kinases and substrates. Recently, competitive chemical proteomics has emerged as a complementary, unbiased, cell-based methodology to define the target landscape of kinase inhibitors. Here, we evaluated and optimized a competitive multiplexed inhibitor bead mass spectrometry (MIB/MS) platform using cell lysates, live cells, and treated mice...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29123178/a-nanobody-based-tracer-targeting-dpp6-for-non-invasive-imaging-of-human-pancreatic-endocrine-cells
#5
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/29115211/measurement-of-gastrointestinal-hormones
#6
Nicolai J Wewer Albrechtsen
Towards the end of the 20th century, the number of subjects with diabetes and obesity rose exponentially. The discoveries of insulin- and appetite-modulating chemical signals, including glucagon-like peptide-1 (GLP-1), secreted from the gastrointestinal system, led to development of a new group of drugs which now are being used for glucose-lowering therapy and weight loss. Understanding of the physiology of gut derived signals and their pathophysiologi-cal importance requires accurate measurements of their circulat-ing levels...
November 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/29083510/on-the-etiology-of-type-1-diabetes-physiological-growth-in-children-impacts-disease-progression
#7
REVIEW
Oskar Skog, Olle Korsgren
The prevailing view is that Type 1 Diabetes (T1D) develops as a consequence of a severe fall in beta-cell mass resulting from T-cell mediated autoimmunity. However, progression from islet autoantibody seroconversion to overt diabetes and finally to total loss of c-peptide production occurs in most affected subjects only slowly over many years or even decades. This slow disease progression should be viewed in relation to the total beta cell mass of only 0.2 - 1.5 g in non-diabetic adults. Focal lesions of acute pancreatitis with accumulation of leukocytes, often located around the ducts, are frequently observed in subjects with recent onset T1D and most patients display extensive periductal fibrosis, the end stage of inflammation...
October 30, 2017: Diabetes, Obesity & Metabolism
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/29075301/insulinoma-masquerading-as-a-loss-of-consciousness-in-a-teenage-girl-case-report-and-literature-review
#9
Meghana Gudala, Mahmuda Ahmed, Rushika Conroy, Ksenia Tonyushkina
BACKGROUND: Hypoglycemia due to a pancreatic beta cell neoplasm - insulinoma, is uncommon with only a few cases described. We report on a previously healthy 15-year-old Hispanic female with insulinoma who presented with a loss of consciousness due to hypoglycemia unawareness. CASE PRESENTATION: EM was first brought to the emergency department (ED) after she was found unresponsive at home with point of care (POC) glucose of 29 mg/dL(1.6 mmol/L) documented by emergency medical services (EMS) upon arrival...
2017: International Journal of Pediatric Endocrinology
https://www.readbyqxmd.com/read/29068758/effects-of-biotin-supplementation-during-the-first-week-postweaning-increases-pancreatic-islet-area-beta-cell-proportion-islets-number-and-beta-cell-proliferation
#10
Wilma Tixi-Verdugo, Juan Contreras-Ramos, Gloria Sicilia-Argumedo, Michael S German, Cristina Fernandez-Mejia
During maturation, pancreatic islets achieve their full capacity to secrete insulin in response to glucose, undergo morphological changes in which alpha-cells decrease and beta-cell mass increases, and they acquire the normal alpha- and beta-cell proportion changes that are important for islet functions later in life. In rodents, the first week of postweaning is critical for islet maturation. Multiple studies have documented the detrimental effects of several conditions on pancreatic maturation; however, few studies have addressed the use of pharmacological agents to enhance islet maturation...
October 25, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29065151/g-protein-coupled-estrogen-receptor-regulates-embryonic-heart-rate-in-zebrafish
#11
Shannon N Romano, Hailey E Edwards, Jaclyn Paige Souder, Kevin J Ryan, Xiangqin Cui, Daniel A Gorelick
Estrogens act by binding to estrogen receptors alpha and beta (ERα, ERβ), ligand-dependent transcription factors that play crucial roles in sex differentiation, tumor growth and cardiovascular physiology. Estrogens also activate the G protein-coupled estrogen receptor (GPER), however the function of GPER in vivo is less well understood. Here we find that GPER is required for normal heart rate in zebrafish embryos. Acute exposure to estrogens increased heart rate in wildtype and in ERα and ERβ mutant embryos but not in GPER mutants...
October 2017: PLoS Genetics
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
#12
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/29058819/involvement-of-dying-beta-cell-originated-messenger-molecules-in-differentiation-of-pancreatic-mesenchymal-stem-cells-under-glucotoxic-and-glucolipotoxic-conditions
#13
Selda Gezginci-Oktayoglu, Evren Onay-Ucar, Serap Sancar-Bas, Ayse Karatug-Kacar, Emine Sekure Nazli Arda, Sehnaz Bolkent
Beta cell mass regulation represents a critical issue for understanding and treatment of diabetes. The most important process in the development of diabetes is beta cell death, generally induced by glucotoxicity or glucolipotoxicity, and the regeneration mechanism of new beta cells that will replace dead beta cells is still not fully understood. The aim of this study was to investigate the generation mechanism of new beta cells by considering the compensation phase of type2 diabetes mellitus. Pancreatic islet derived mesenchymal stem cells (PI-MSCs) were isolated from adult rats and characterized...
October 23, 2017: Journal of Cellular Physiology
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
#14
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/29051963/applications-of-particulate-oxygen-generating-substances-pogs-in-the-bioartificial-pancreas
#15
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/29040630/assessment-of-beta-cell-mass-and-function-by-airmax-and-ivgtt-in-high-risk-subjects-for-type-1-diabetes
#16
Wei Hao, Alyssa Wookwyk, Craig Beam, Tee Bahnson, Jerry P Palmer, Carla J Greenbaum
Context: There is little information regarding beta cell mass in individuals at early stages of type 1 diabetes (T1D). Objective: To investigate both AIRmax, as a correlate of beta cell mass, and beta cell function by IVGTT in subjects at early stages of T1D. Design/Setting/Participants: Forty subjects were enrolled: (1) low risk group: relatives of patients with T1D with 0-1 antibody (n=21) and (2) high risk group: relatives with > 2 antibodies (n=19)...
October 12, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29040320/circulating-microrna-375-as-biomarker-of-pancreatic-beta-cell-death-and-protection-of-beta-cell-mass-by-cytoprotective-compounds
#17
Imane Song, Sarah Roels, Geert A Martens, Luc Bouwens
OBJECTIVE: Previous studies demonstrated that circulating microRNA-375 (miR-375) is a suitable plasma biomarker for real-time detection of beta cell death. The present study evaluated the use of this biomarker to assess the beta cytoprotective effect of phenylpropenoic acid glucoside (PPAG), which was previously demonstrated to protect beta cells against various types of injury, and of exendin-4, which is an established antidiabetic drug. METHODS: PPAG or exendin-4 were administered in mice treated with streptozotocin (STZ) to acutely induce beta cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29038309/deletion-of-protein-kinase-d1-in-pancreatic-beta-cells-impairs-insulin-secretion-in-high-fat-fed-mice
#18
Valérie Bergeron, Julien Ghislain, Kevin Vivot, Natalia Tamarina, Louis H Philipson, Jens Fielitz, Vincent Poitout
Beta-cell adaptation to insulin resistance is necessary to maintain glucose homeostasis in obesity. Failure of this mechanism is a hallmark of type 2 diabetes (T2D). Hence, factors controlling functional beta-cell compensation are potentially important targets for the treatment of T2D. Protein kinase D1 (PKD1) integrates diverse signals in the beta cell and plays a critical role in the control of insulin secretion. However, the role of beta-cell PKD1 in glucose homeostasis in vivo is essentially unknown. Using beta-cell specific, inducible PKD1 knock-out mice (βPKD1KO), we examined the role of beta-cell PKD1 under basal conditions and during high-fat feeding...
October 16, 2017: Diabetes
https://www.readbyqxmd.com/read/29026710/factors-associated-with-c-peptide-levels-after-diagnosis-in-children-with-type-1-diabetes-mellitus
#19
Jung Won Hwang, Min Sun Kim, Dae-Yeol Lee
C-peptide is the best indicator of endogenous insulin secretion in patients with diabetes. This study investigated the relationship between C-peptide levels and clinical/laboratory parameters of children with type 1 diabetes mellitus (T1DM), as measured at 6-month intervals after diagnosis. We retrospectively reviewed the data of 34 children with newly diagnosed T1DM. The study subjects were subdivided into a rapid progression group with C-peptide levels <0.6 ng/mL at 36 months (n=27; Group A) and a slow progression group with C-peptide levels >0...
September 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/29020885/identification-of-pa28%C3%AE-as-a-potential-novel-biomarker-in-human-esophageal-squamous-cell-carcinoma
#20
Jin-Yan Chen, Li Xu, Wei-Min Fang, Jun-Yong Han, Kun Wang, Kun-Shou Zhu
Esophageal squamous cell carcinoma (ESCC) is one of the most common and serious malignancies in China. However, the exact mechanisms of tumor formation and progression are unclear. As late diagnosis and poor therapeutic efficacy result in lower survival rates, identifying biomarkers for early detection, prognostic evaluation, and recurrence monitoring of ESCC is necessary. Here we analyzed 10 protein expression profiles of ESCC core tissues and paired normal esophageal epithelial tissues using two-dimensional gel electrophoresis...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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