1,228 results match your criteria susceptibility islet


Type I interferons as key players in pancreatic β-cell dysfunction in type 1 diabetes.

Int Rev Cell Mol Biol 2021 23;359:1-80. Epub 2021 Mar 23.

Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández, Elche, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by pancreatic islet inflammation (insulitis) and specific pancreatic β-cell destruction by an immune attack. Although the precise underlying mechanisms leading to the autoimmune assault remain poorly understood, it is well accepted that insulitis takes place in the context of a conflicting dialogue between pancreatic β-cells and the immune cells. Moreover, both host genetic background (i. Read More

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Associations of breastfeeding with childhood autoimmunity, allergies, and overweight: The Environmental Determinants of Diabetes in the Young (TEDDY) study.

Am J Clin Nutr 2021 Apr 8. Epub 2021 Apr 8.

Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany; and Forschergruppe Diabetes, Technical University Munich, at Klinikum rechts der Isar, Munich, and Forschergruppe Diabetes eV, Neuherberg, Germany.

Background: Breastfeeding has beneficial effects on numerous health outcomes.

Objectives: We investigated whether breastfeeding duration is associated with the development of early childhood autoimmunity, allergies, or obesity in a multinational prospective birth cohort.

Methods: Infants with genetic susceptibility for type 1 diabetes (n = 8676) were followed for the development of autoantibodies to islet autoantigens or transglutaminase, allergies, and for anthropometric measurements to a median age of 8. Read More

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Inherent Beta Cell Dysfunction Contributes to Autoimmune Susceptibility.

Biomolecules 2021 Mar 30;11(4). Epub 2021 Mar 30.

Barbara Davis Center for Diabetes, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA.

The pancreatic beta cell is a highly specialized cell type whose primary function is to secrete insulin in response to nutrients to maintain glucose homeostasis in the body. As such, the beta cell has developed unique metabolic characteristics to achieve functionality; in healthy beta cells, the majority of glucose-derived carbons are oxidized and enter the mitochondria in the form of pyruvate. The pyruvate is subsequently metabolized to induce mitochondrial ATP and trigger the downstream insulin secretion response. Read More

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Case of slowly progressive type 1 diabetes mellitus with drastically reduced insulin secretory capacity after immune checkpoint inhibitor treatment for advanced renal cell carcinoma.

Diabetol Int 2021 Apr 24;12(2):234-240. Epub 2020 Aug 24.

Department of Diabetes and Endocrinology, Osaka Police Hospital, 10-31 Kitayama-cho Tennoujiku, Osaka, 543-0035 Japan.

We encountered a 55-year-old Japanese man with advanced renal cell carcinoma and slowly progressive type 1 diabetes mellitus (SPT1DM), whose insulin secretory capacity was drastically reduced for a brief period after only one cycle of immune checkpoint inhibitor (ICI) treatment. The patient had been diagnosed with type 2 diabetes at the age of 53 years and was treated using oral hypoglycemic agents. However, 2 years later, he was diagnosed with SPT1DM and autoimmune thyroiditis, based on the presence of anti-glutamic acid decarboxylase antibodies (GADA) and thyroid autoantibodies, which was accompanied by advanced renal cell carcinoma. Read More

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Perilipin2 down-regulation in β cells impairs insulin secretion under nutritional stress and damages mitochondria.

JCI Insight 2021 Mar 30. Epub 2021 Mar 30.

Department of Internal Medicine, University of Iowa, Iowa City, United States of America.

Perilipin 2 (PLIN2) is the lipid droplet (LD) protein in β cells that increases under nutritional stress. Down-regulation of PLIN2 is often sufficient to reduce LD accumulation. To determine whether PLIN2 positively or negatively affects β cell function under nutritional stress, PLIN2 was down-regulated in mouse β cells, INS1 cells, and human islet cells. Read More

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Type 1 diabetes mellitus: much progress, many opportunities.

Authors:
Alvin C Powers

J Clin Invest 2021 Mar 24. Epub 2021 Mar 24.

Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America.

As part of the centennial celebration of insulin's discovery, this review summarizes the current understanding of the genetics, pathogenesis, treatment, and outcomes in type 1 diabetes (T1D). T1D results from an autoimmune response that leads to destruction of the β cells in the pancreatic islet and requires life-long insulin therapy. While much has been learned about T1D, it is now clear that there is considerable heterogeneity in T1D with regards to genetics, pathology, response to immune-based therapies, clinical course, and susceptibility to diabetes-related complications. Read More

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Islet isograft transplantation improves insulin sensitivity in a murine model of type 2 diabetes.

Endocrine 2021 Mar 12. Epub 2021 Mar 12.

Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Purpose: Type 2 diabetes develops in the presence of chronic overnutrition and genetic susceptibility, and causes insulin resistance and relative insulin deficiency. We hypothesized that islet transplantation can improve insulin sensitivity by modifying the mediators of insulin sensitivity in the pancreas, liver, muscle, and adipose tissues.

Methods: Eight-week-old male mice were used as both recipients and donors in this study. Read More

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The central role of glutathione peroxidase 4 in the regulation of ferroptosis and its implications for pro-inflammatory cytokine-mediated beta-cell death.

Biochim Biophys Acta Mol Basis Dis 2021 Jun 2;1867(6):166114. Epub 2021 Mar 2.

Institute of Clinical Biochemistry, Hannover Medical School, 30625, Hannover, Germany. Electronic address:

Pro-inflammatory cytokines are crucial mediators of beta-cell destruction in type 1 diabetes mellitus (T1DM). The involvement of ferroptosis as a form of oxidative non-apoptotic cell death in T1DM pathogenesis has not been elucidated so far. Moreover, the role of glutathione peroxidase 4 (GPx4) as an antioxidative enzyme and a major regulator of ferroptosis remains elusive. Read More

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Analysis of opacification patterns in intraocular lenses (IOL).

BMJ Open Ophthalmol 2021 11;6(1):e000589. Epub 2021 Feb 11.

Ophthalmology, Universitätsklinikum Ulm, Ulm, Baden-Württemberg, Germany.

Objective: Intraocular lens (IOL) opacification may cause severe visual impairment. The pathogenesis remains unclear. The aim of this study was to analyse opacification patterns in different IOLs. Read More

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February 2021

Long Non-Coding RNAs as Key Modulators of Pancreatic β-Cell Mass and Function.

Front Endocrinol (Lausanne) 2020 8;11:610213. Epub 2021 Feb 8.

Section of Cell Biology and Functional Genomics, Division of Diabetes Endocrinology and Diabetes, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.

Numerous studies have sought to decipher the genetic and other mechanisms contributing to β-cell loss and dysfunction in diabetes mellitus. However, we have yet to fully understand the etiology of the disease or to develop satisfactory treatments. Since the majority of diabetes susceptibility are mapped to non-coding regions within the genome, understanding the functions of non-coding RNAs in β-cell biology might provide crucial insights into the pathogenesis of type 1 (T1D) and type 2 (T2D) diabetes. Read More

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February 2021

An Age-Related Exponential Decline in the Risk of Multiple Islet Autoantibody Seroconversion During Childhood.

Diabetes Care 2021 Feb 24. Epub 2021 Feb 24.

National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.

Objective: Islet autoimmunity develops before clinical type 1 diabetes and includes multiple and single autoantibody phenotypes. The objective was to determine age-related risks of islet autoantibodies that reflect etiology and improve screening for presymptomatic type 1 diabetes.

Research Design And Methods: The Environmental Determinants of Diabetes in the Young study prospectively monitored 8,556 genetically at-risk children at 3- to 6-month intervals from birth for the development of islet autoantibodies and type 1 diabetes. Read More

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February 2021

Studying the heterogeneous pathogenesis of canine diabetes: Observational characterization of an island population.

Vet Med Sci 2021 Feb 23. Epub 2021 Feb 23.

Instituto Universitario de Investigaciones Biomédicas y Sanitarias, Universidad de Las Palmas de Gran Canaria (ULPGC), Las Palmas de Gran Canaria, Spain.

Background: Canine diabetes mellitus has mostly been studied in northern European, Australian and American populations, whereas other regions have received less attention.

Objectives: We evaluated the epidemiological, clinical and histopathological features of diabetic dogs in Gran Canaria, Spain.

Methods: Prevalence and incidence were estimated. Read More

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February 2021

SNPs in the 3'-untranslated region of confer risk of type 2 diabetes mellitus in a south-east Iranian population: Evidences from case-control and bioinformatics studies.

J Diabetes Metab Disord 2020 Dec 21;19(2):979-988. Epub 2020 Jul 21.

Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: Type 2 diabetes mellitus (T2DM) is a heterogenic disease with increasing incidence. The gene encodes an islet zinc transporter (ZnT8), and its variants have been associated with glucose and pro-insulin levels. This study was aimed to examine the effects of a missense variant (rs13266634 C/T), and two 3'UTR variants (rs2466294 C/G and rs2466293 T/C) in gene on T2DM risk in a south-east Iranian population. Read More

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December 2020

Circular RNAs as Novel Regulators of β-Cell Functions under Physiological and Pathological Conditions.

Int J Mol Sci 2021 Feb 3;22(4). Epub 2021 Feb 3.

Department of Fundamental Neurosciences, University of Lausanne, 1005 Lausanne, Switzerland.

Circular RNAs (circRNAs) constitute a large class of non-coding RNAs characterized by a covalently closed circular structure. They originate during mRNA maturation through a modification of the splicing process and, according to the included sequences, are classified as Exonic, Intronic, or Exonic-Intronic. CircRNAs can act by sequestering microRNAs, by regulating the activity of specific proteins, and/or by being translated in functional peptides. Read More

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February 2021

Serum fatty acids and risk of developing islet autoimmunity: A nested case-control study within the TRIGR birth cohort.

Pediatr Diabetes 2021 Feb 5. Epub 2021 Feb 5.

Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland.

Background: Circulating fatty acids have been linked to development of type 1 diabetes.

Objectives: To study the prospective associations of serum fatty acids with the risk of islet autoimmunity in high-risk children.

Methods: A nested case-control selection was carried out within the TRIGR cohort, which included infants with HLA (DQB1 or DQA1)-conferred disease susceptibility and a first-degree relative with type 1 diabetes, born between 2002 and 2007 in 15 countries and followed-up until 2017. Read More

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February 2021

Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning.

Authors:
Daniel J Drucker

Cell Metab 2021 03 21;33(3):479-498. Epub 2021 Jan 21.

Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, 600 University Avenue, Toronto, ON M5G 1X5, Canada. Electronic address:

The increased prevalence of obesity, diabetes, and cardiovascular risk factors in people hospitalized with severe COVID-19 illness has engendered considerable interest in the metabolic aspects of SARS-CoV-2-induced pathophysiology. Here, I update concepts informing how metabolic disorders and their co-morbidities modify the susceptibility to, natural history, and potential treatment of SARS-CoV-2 infection, with a focus on human biology. New data informing genetic predisposition, epidemiology, immune responses, disease severity, and therapy of COVID-19 in people with obesity and diabetes are highlighted. Read More

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Modulating glutathione thiol status alters pancreatic β-cell morphogenesis in the developing zebrafish (Danio rerio) embryo.

Redox Biol 2021 Jan 6;38:101788. Epub 2020 Nov 6.

Molecular & Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, 01003, USA; Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, 01003, USA. Electronic address:

Emerging evidence suggests that redox-active chemicals perturb pancreatic islet development. To better understand potential mechanisms for this, we used zebrafish (Danio rerio) embryos to investigate roles of glutathione (GSH; predominant cellular redox buffer) and the transcription factor Nrf2a (Nfe2l2a; zebrafish Nrf2 co-ortholog) in islet morphogenesis. We delineated critical windows of susceptibility to redox disruption of β-cell morphogenesis, interrogating embryos at 24, 48 and 72 h post fertilization (hpf) and visualized Nrf2a expression in the pancreas using whole-mount immunohistochemistry at 96 hpf. Read More

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January 2021

Checking the Checkpoint Inhibitors: A Case of Autoimmune Diabetes After PD-1 Inhibition in a Patient with HIV.

J Endocr Soc 2020 Dec 12;4(12):bvaa150. Epub 2020 Nov 12.

Baylor College of Medicine, Houston, Texas, USA.

Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a known immune-related adverse event (irAE) following treatment with programmed cell death protein 1 (PD-1), with a reported 0.9% incidence. We hereby present the first case, to our knowledge, of ICI-DM following ICI use in a human immunodeficiency virus (HIV) patient. Read More

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December 2020

Long noncoding RNAs as novel biomarkers for Type 2 diabetes.

Biomark Med 2020 10 6;14(15):1501-1511. Epub 2020 Nov 6.

Department of Pharmacy, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai 201399, China.

Type 2 diabetes (T2D) is a metabolic disease characterized by disordered glucagon secretion, insulin resistance in target tissues, and decreased islet β-cell mass and function. The routine diagnosis was based on measurements of metabolic markers, while genetic risk factors have been considered to increase the probability of predicting the development of the disease. Recent evidence suggests that long noncoding RNAs (lncRNAs) regulate gene expression in various physiological and pathological processes. Read More

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October 2020

Novel genetic risk factors influence progression of islet autoimmunity to type 1 diabetes.

Sci Rep 2020 11 5;10(1):19193. Epub 2020 Nov 5.

Center for Public Health Genomics, University of Virginia, PO Box 800717, Charlottesville, VA, 22908, USA.

Type 1 diabetes arises from the autoimmune destruction of insulin-producing beta-cells of the pancreas, resulting in dependence on exogenously administered insulin to maintain glucose homeostasis. In this study, our aim was to identify genetic risk factors that contribute to progression from islet autoimmunity to clinical type 1 diabetes. We analyzed 6. Read More

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November 2020

Prediction of the development of islet autoantibodies through integration of environmental, genetic, and metabolic markers.

J Diabetes 2021 Feb 16;13(2):143-153. Epub 2020 Aug 16.

Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Background: The Environmental Determinants of the Diabetes in the Young (TEDDY) study has prospectively followed, from birth, children at increased genetic risk of type 1 diabetes. TEDDY has collected heterogenous data longitudinally to gain insights into the environmental and biological mechanisms driving the progression to persistent islet autoantibodies.

Methods: We developed a machine learning model to predict imminent transition to the development of persistent islet autoantibodies based on time-varying metabolomics data integrated with time-invariant risk factors (eg, gestational age). Read More

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February 2021

Presumption of guilt for T cells in type 1 diabetes: lead culprits or partners in crime depending on age of onset?

Diabetologia 2021 Jan 21;64(1):15-25. Epub 2020 Oct 21.

Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France.

Available evidence provides arguments both for and against a primary pathogenic role for T cells in human type 1 diabetes. Genetic susceptibility linked to HLA Class II lends strong support. Histopathology documents HLA Class I hyperexpression and islet infiltrates dominated by CD8 T cells. Read More

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January 2021

Female mice exposed to low doses of dioxin during pregnancy and lactation have increased susceptibility to diet-induced obesity and diabetes.

Mol Metab 2020 12 16;42:101104. Epub 2020 Oct 16.

Department of Biology and Institute of Biochemistry, Carleton University, Ottawa, ON, Canada. Electronic address:

Objective: Exposure to persistent organic pollutants is consistently associated with increased diabetes risk in humans. We investigated the short- and long-term impact of transient low-dose dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) exposure during pregnancy and lactation on glucose homeostasis and beta cell function in female mice, including their response to a metabolic stressor later in life.

Methods: Female mice were injected with either corn oil (CO; vehicle control) or 20 ng/kg/d TCDD 2x/week throughout mating, pregnancy and lactation, and then tracked for 6-10 weeks after chemical exposure stopped. Read More

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December 2020

Association between family history, early growth and the risk of beta cell autoimmunity in children at risk for type 1 diabetes.

Diabetologia 2021 Jan 7;64(1):119-128. Epub 2020 Oct 7.

Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Aims/hypothesis: The aim of this work was to examine the relationship between family history of type 1 diabetes, birthweight, growth during the first 2 years and development of multiple beta cell autoantibodies in children with a first-degree relative with type 1 diabetes and HLA-conferred disease susceptibility.

Methods: In a secondary analysis of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), clinical characteristics and development of beta cell autoantibodies were compared in relation to family history of type 1 diabetes (mother vs father vs sibling) in 2074 children from families with a single affected family member.

Results: Multiple autoantibodies (≥2 of 5 measured) developed in 277 (13%) children: 107 (10%), 114 (16%) and 56 (18%) born with a mother, father or sibling with type 1 diabetes, respectively (p < 0. Read More

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January 2021

CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation.

Front Immunol 2020 4;11:2180. Epub 2020 Sep 4.

Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL, United States.

The costimulatory molecule CD226 is highly expressed on effector/memory T cells and natural killer cells. Costimulatory signals received by T cells can impact both central and peripheral tolerance mechanisms. Genetic polymorphisms in have been associated with susceptibility to type 1 diabetes and other autoimmune diseases. Read More

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September 2020

Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D.

Nat Commun 2020 09 30;11(1):4912. Epub 2020 Sep 30.

Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.

Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. Read More

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September 2020

Mechanisms of Congenital Malformations in Pregnancies with Pre-existing Diabetes.

Authors:
Mary R Loeken

Curr Diab Rep 2020 09 12;20(10):54. Epub 2020 Sep 12.

Section on Islet Cell and Regenerative Biology, Department of Medicine, Joslin Diabetes Center and Harvard Medical School, One Joslin Place, Boston, MA, 02215, USA.

Purpose Of Review: Fetuses of diabetic mothers are at increased risk for congenital malformations. Research in recent decades using animal and embryonic stem cell models has revealed many embryonic developmental processes that are disturbed by maternal diabetes. The aim of this review is to give clinicians a better understanding of the reasons for rigorous glycemic control in early pregnancy, and to provide background to guide future research. Read More

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September 2020

Molecular and functional profiling of human islets: from heterogeneity to human phenotypes.

Diabetologia 2020 10 7;63(10):2095-2101. Epub 2020 Sep 7.

Department of Pharmacology, University of Alberta, Edmonton, AB, Canada.

Efforts to phenotype pancreatic islets have contributed tremendously to our present understanding of endocrine function and diabetes. A continued evolution in approaches to study islet physiology is important given the need to establish reference points for mature islet functionality, understanding biological variation amongst individuals and cells, and the ongoing appreciation of the role for islets in diabetes susceptibility. Recent efforts in islet biology have focused on technological improvements in imaging, molecular profiling and data analysis, along with a push for enhanced transparency and reporting. Read More

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October 2020

Dynamics of Islet Autoantibodies During Prospective Follow-Up From Birth to Age 15 Years.

J Clin Endocrinol Metab 2020 12;105(12)

Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Context: We set out to characterize the dynamics of islet autoantibodies over the first 15 years of life in children carrying genetic susceptibility to type 1 diabetes (T1D). We also assessed systematically the role of zinc transporter 8 autoantibodies (ZnT8A) in this context.

Design: HLA-predisposed children (N = 1006, 53. Read More

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December 2020