ArticleEndocrinology2015
An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes.
Open access · bronzeAbstract read
In one paragraph
Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 4% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Adipose Tissue Epigenetic Profile in Obesity-Related Dysglycemia - A Systematic Review.Frontiers in endocrinology · 2021Pooled it
- Evidence for a Cytokine-Sensitive Network of Iron-Associated Genes That Protects Pancreatic Islets Against Ferroptosis.Metabolites · 2026Article
- XIAP down-regulation inhibits RIPK2 ubiquitination-mediated insulin resistance.Endocrine connections · 2026Article
- NEDD4 facilitates the progression of endometrial carcinoma by enhancing PAMR1 protein degradation through ubiquitination.Functional & integrative genomics · 2025Article
- Diabetes-Mediated STEAP4 Enhances Retinal Oxidative Stress and Impacts the Development of Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2025Article
- Inflammatory response in gastrointestinal cancers: Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications.World journal of clinical oncology · 2024Review
- The Role of STAMP2 in Pathogenesis of Chronic Diseases Focusing on Nonalcoholic Fatty Liver Disease: A Review.Biomedicines · 2022Review
- Synchrotron fluorescence imaging of individual mouse beta-cells reveals changes in zinc, calcium, and iron in a model of low-grade inflammation.Metallomics : integrated biometal science · 2021Article
- High Expression of PAMR1 Predicts Favorable Prognosis and Inhibits Proliferation, Invasion, and Migration in Cervical Cancer.Frontiers in oncology · 2021Article
- Reflections on undergraduate research mentoring.Biophysicist (Rockville, Md.) · 2020Article
- STEAP4 Inhibits HIF-1α/PKM2 Signaling and Reduces High Glucose-Induced Apoptosis of Retinal Vascular Endothelial Cells.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020Article
- JUND regulates pancreatic β cell survival during metabolic stress.Molecular metabolism · 2019Article
- TMT Based Proteomic Analysis of Human Follicular Fluid From Overweight/Obese and Normal-Weight Patients With Polycystic Ovary Syndrome.Frontiers in endocrinology · 2019Article
- Cytokine-mediated changes in KScientific reports · 2018Article
- Metformin Inhibits Mouse Islet Insulin Secretion and Alters Intracellular Calcium in a Concentration-Dependent and Duration-Dependent Manner near the Circulating Range.Journal of diabetes research · 2018Article
- STAMP2 is required for human adipose-derived stem cell differentiation and adipocyte-facilitated prostate cancer growthOncotarget · 2017Article
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- STEAP4: its emerging role in metabolism and homeostasis of cellular iron and copper.The Journal of endocrinology · 2017Review
- STEAP4 expression in human islets is associated with differences in body mass index, sex, HbA1c, and inflammation.Endocrine · 2017Article
- Androgen receptor-deficient islet β-cells exhibit alteration in genetic markers of insulin secretion and inflammation. A transcriptome analysis in the male mouse.Journal of diabetes and its complications · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Poonam R SharmaDepartment of Medicine (P.R.S., E.A.D., J.W.R., C.S.N.), Center for Public Health Genomics (A.J.M., S.S.R.), and Department of Chemistry (E.A.D.), University of Virginia, Charlottesville, Virginia 22904; Department of Biochemistry (N.D.P.), Center for Genomics and Personalized Medicine Research (N.D.P.), Center for Diabetes Research (N.D.P.), Center for Public Health Genomics (C.D.L., N.D.P., L.E.W.), Department of Biostatistical Sciences (C.D.L.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157; Department of Physiology and Biophysics (R.M.W.), Department of Preventive Medicine, and USC Diabetes and Obesity Research Institute (R.M.W.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033; and Institute for Translational Genomics and Population Sciences (K.D.T.) and Department of Pediatrics (K.D.T.), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502.
Aaron J MackeyDepartment of Medicine (P.R.S., E.A.D., J.W.R., C.S.N.), Center for Public Health Genomics (A.J.M., S.S.R.), and Department of Chemistry (E.A.D.), University of Virginia, Charlottesville, Virginia 22904; Department of Biochemistry (N.D.P.), Center for Genomics and Personalized Medicine Research (N.D.P.), Center for Diabetes Research (N.D.P.), Center for Public Health Genomics (C.D.L., N.D.P., L.E.W.), Department of Biostatistical Sciences (C.D.L.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157; Department of Physiology and Biophysics (R.M.W.), Department of Preventive Medicine, and USC Diabetes and Obesity Research Institute (R.M.W.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033; and Institute for Translational Genomics and Population Sciences (K.D.T.) and Department of Pediatrics (K.D.T.), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502.
Eden A DejeneDepartment of Medicine (P.R.S., E.A.D., J.W.R., C.S.N.), Center for Public Health Genomics (A.J.M., S.S.R.), and Department of Chemistry (E.A.D.), University of Virginia, Charlottesville, Virginia 22904; Department of Biochemistry (N.D.P.), Center for Genomics and Personalized Medicine Research (N.D.P.), Center for Diabetes Research (N.D.P.), Center for Public Health Genomics (C.D.L., N.D.P., L.E.W.), Department of Biostatistical Sciences (C.D.L.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157; Department of Physiology and Biophysics (R.M.W.), Department of Preventive Medicine, and USC Diabetes and Obesity Research Institute (R.M.W.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033; and Institute for Translational Genomics and Population Sciences (K.D.T.) and Department of Pediatrics (K.D.T.), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502.
James W RamadanDepartment of Medicine (P.R.S., E.A.D., J.W.R., C.S.N.), Center for Public Health Genomics (A.J.M., S.S.R.), and Department of Chemistry (E.A.D.), University of Virginia, Charlottesville, Virginia 22904; Department of Biochemistry (N.D.P.), Center for Genomics and Personalized Medicine Research (N.D.P.), Center for Diabetes Research (N.D.P.), Center for Public Health Genomics (C.D.L., N.D.P., L.E.W.), Department of Biostatistical Sciences (C.D.L.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157; Department of Physiology and Biophysics (R.M.W.), Department of Preventive Medicine, and USC Diabetes and Obesity Research Institute (R.M.W.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033; and Institute for Translational Genomics and Population Sciences (K.D.T.) and Department of Pediatrics (K.D.T.), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502.
Carl D LangefeldDepartment of Medicine (P.R.S., E.A.D., J.W.R., C.S.N.), Center for Public Health Genomics (A.J.M., S.S.R.), and Department of Chemistry (E.A.D.), University of Virginia, Charlottesville, Virginia 22904; Department of Biochemistry (N.D.P.), Center for Genomics and Personalized Medicine Research (N.D.P.), Center for Diabetes Research (N.D.P.), Center for Public Health Genomics (C.D.L., N.D.P., L.E.W.), Department of Biostatistical Sciences (C.D.L.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157; Department of Physiology and Biophysics (R.M.W.), Department of Preventive Medicine, and USC Diabetes and Obesity Research Institute (R.M.W.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033; and Institute for Translational Genomics and Population Sciences (K.D.T.) and Department of Pediatrics (K.D.T.), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502.
Nicholette D PalmerDepartment of Medicine (P.R.S., E.A.D., J.W.R., C.S.N.), Center for Public Health Genomics (A.J.M., S.S.R.), and Department of Chemistry (E.A.D.), University of Virginia, Charlottesville, Virginia 22904; Department of Biochemistry (N.D.P.), Center for Genomics and Personalized Medicine Research (N.D.P.), Center for Diabetes Research (N.D.P.), Center for Public Health Genomics (C.D.L., N.D.P., L.E.W.), Department of Biostatistical Sciences (C.D.L.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157; Department of Physiology and Biophysics (R.M.W.), Department of Preventive Medicine, and USC Diabetes and Obesity Research Institute (R.M.W.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033; and Institute for Translational Genomics and Population Sciences (K.D.T.) and Department of Pediatrics (K.D.T.), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502.
Kent D TaylorDepartment of Medicine (P.R.S., E.A.D., J.W.R., C.S.N.), Center for Public Health Genomics (A.J.M., S.S.R.), and Department of Chemistry (E.A.D.), University of Virginia, Charlottesville, Virginia 22904; Department of Biochemistry (N.D.P.), Center for Genomics and Personalized Medicine Research (N.D.P.), Center for Diabetes Research (N.D.P.), Center for Public Health Genomics (C.D.L., N.D.P., L.E.W.), Department of Biostatistical Sciences (C.D.L.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157; Department of Physiology and Biophysics (R.M.W.), Department of Preventive Medicine, and USC Diabetes and Obesity Research Institute (R.M.W.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033; and Institute for Translational Genomics and Population Sciences (K.D.T.) and Department of Pediatrics (K.D.T.), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502.
Lynne E WagenknechtDepartment of Medicine (P.R.S., E.A.D., J.W.R., C.S.N.), Center for Public Health Genomics (A.J.M., S.S.R.), and Department of Chemistry (E.A.D.), University of Virginia, Charlottesville, Virginia 22904; Department of Biochemistry (N.D.P.), Center for Genomics and Personalized Medicine Research (N.D.P.), Center for Diabetes Research (N.D.P.), Center for Public Health Genomics (C.D.L., N.D.P., L.E.W.), Department of Biostatistical Sciences (C.D.L.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157; Department of Physiology and Biophysics (R.M.W.), Department of Preventive Medicine, and USC Diabetes and Obesity Research Institute (R.M.W.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033; and Institute for Translational Genomics and Population Sciences (K.D.T.) and Department of Pediatrics (K.D.T.), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502.
Richard M WatanabeDepartment of Medicine (P.R.S., E.A.D., J.W.R., C.S.N.), Center for Public Health Genomics (A.J.M., S.S.R.), and Department of Chemistry (E.A.D.), University of Virginia, Charlottesville, Virginia 22904; Department of Biochemistry (N.D.P.), Center for Genomics and Personalized Medicine Research (N.D.P.), Center for Diabetes Research (N.D.P.), Center for Public Health Genomics (C.D.L., N.D.P., L.E.W.), Department of Biostatistical Sciences (C.D.L.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157; Department of Physiology and Biophysics (R.M.W.), Department of Preventive Medicine, and USC Diabetes and Obesity Research Institute (R.M.W.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033; and Institute for Translational Genomics and Population Sciences (K.D.T.) and Department of Pediatrics (K.D.T.), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502.
Stephen S RichDepartment of Medicine (P.R.S., E.A.D., J.W.R., C.S.N.), Center for Public Health Genomics (A.J.M., S.S.R.), and Department of Chemistry (E.A.D.), University of Virginia, Charlottesville, Virginia 22904; Department of Biochemistry (N.D.P.), Center for Genomics and Personalized Medicine Research (N.D.P.), Center for Diabetes Research (N.D.P.), Center for Public Health Genomics (C.D.L., N.D.P., L.E.W.), Department of Biostatistical Sciences (C.D.L.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157; Department of Physiology and Biophysics (R.M.W.), Department of Preventive Medicine, and USC Diabetes and Obesity Research Institute (R.M.W.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033; and Institute for Translational Genomics and Population Sciences (K.D.T.) and Department of Pediatrics (K.D.T.), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502.
Craig S NunemakerDepartment of Medicine (P.R.S., E.A.D., J.W.R., C.S.N.), Center for Public Health Genomics (A.J.M., S.S.R.), and Department of Chemistry (E.A.D.), University of Virginia, Charlottesville, Virginia 22904; Department of Biochemistry (N.D.P.), Center for Genomics and Personalized Medicine Research (N.D.P.), Center for Diabetes Research (N.D.P.), Center for Public Health Genomics (C.D.L., N.D.P., L.E.W.), Department of Biostatistical Sciences (C.D.L.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157; Department of Physiology and Biophysics (R.M.W.), Department of Preventive Medicine, and USC Diabetes and Obesity Research Institute (R.M.W.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033; and Institute for Translational Genomics and Population Sciences (K.D.T.) and Department of Pediatrics (K.D.T.), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502.
Office of Public Health Genomics · USUniversity of Virginia · USHarbor–UCLA Medical Center · US
Funding
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4MGenetics of Beta Cell Failure in Mexican AmericansR01DK061628 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BUCHANAN, THOMAS A, XIANG, ANNY H · 2003 to 2012
$10.0MGenetic & Epidemiologic Predictors of Glucose Homeostasis Measures in HispanicsR01DK085175 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI WAGENKNECHT, LYNNE E, WATANABE, RICHARD M · 2010 to 2013
$6.9MIRAS FAMILY STUDY--GENETICS OF INSULIN RESISTANCER01HL060944 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI WAGENKNECHT, LYNNE E · 1999 to 2009
$5.5MIRAS FAMILY STUDY: GENETICS OF INSULIN RESISTANCER01HL060919 · NHLBI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI LORENZO, CARLOS · 1999 to 2008
$2.7MIRAS FAMILY STUDY--GENETICS OF INSULIN RESISTANCER01HL061019 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI NORRIS, JILL M · 1999 to 2009
$2.6MLow-grade Inflammation, Cytokines, and Beta-Cell Dysfunction in Type 2 DiabetesR01DK089182 · NIDDK · UNIVERSITY OF VIRGINIA · PI NUNEMAKER, CRAIG S · 2011 to 2015
$1.6MAssessing and Improving Pancreatic Islet Viability and FunctionK01DK081621 · NIDDK · UNIVERSITY OF VIRGINIA · PI NUNEMAKER, CRAIG S · 2008 to 2010
$324kINSULIN RESISTANCE AND ATHEROSCLEROSIS STUDY (IRAS)U01HL047887 · NHLBI · WAKE FOREST UNIVERSITY · PI WAGENKNECHT, LYNNE E · 1991 to 1999
–INSULIN RESISTANCE, HYPERGLYCEMIA AND ATHEROSCLEROSISU01HL047889 · NHLBI · KAISER FOUNDATION RESEARCH INSTITUTE · PI SELBY, JOE V · 1991 to 1999
–INSULIN RESISTANCE AND ATHEROSCLEROSIS STUDY (IRAS)U01HL047890 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BERGMAN, RICHARD N. · 1991 to 1999
–NCATS NIH HHS UL1 TR000124NHLBI NIH HHS HL047887NHLBI NIH HHS HL047889NHLBI NIH HHS HL047890NHLBI NIH HHS HL060919NHLBI NIH HHS HL060944NHLBI NIH HHS HL061019NHLBI NIH HHS HL47902NHLBI NIH HHS R01 HL060919NHLBI NIH HHS R01 HL060944NHLBI NIH HHS R01 HL061019NHLBI NIH HHS U01 HL047902NIDDK NIH HHS DK061628NIDDK NIH HHS DK085175NIDDK NIH HHS K01 DK081621NIDDK NIH HHS K01DK081621NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK061628NIDDK NIH HHS R01 DK085175NIDDK NIH HHS R01 DK089182NIDDK NIH HHS R01DK089182
Abstract
Genome-wide association studies in human type 2 diabetes (T2D) have renewed interest in the pancreatic islet as a contributor to T2D risk. Chronic low-grade inflammation resulting from obesity is a risk factor for T2D and a possible trigger of β-cell failure. In this study, microarray data were collected from mouse islets after overnight treatment with cytokines at concentrations consistent with the chronic low-grade inflammation in T2D. Genes with a cytokine-induced change of >2-fold were then examined for associations between single nucleotide polymorphisms and the acute insulin response to glucose (AIRg) using data from the Genetics Underlying Diabetes in Hispanics (GUARDIAN) Consortium. Significant evidence of association was found between AIRg and single nucleotide polymorphisms in Arap3 (5q31.3), F13a1 (6p25.3), Klhl6 (3q27.1), Nid1 (1q42.3), Pamr1 (11p13), Ripk2 (8q21.3), and Steap4 (7q21.12). To assess the potential relevance to islet function, mouse islets were exposed to conditions modeling low-grade inflammation, mitochondrial stress, endoplasmic reticulum (ER) stress, glucotoxicity, and lipotoxicity. RT-PCR revealed that one or more forms of stress significantly altered expression levels of all genes except Arap3. Thapsigargin-induced ER stress up-regulated both Pamr1 and Klhl6. Three genes confirmed microarray predictions of significant cytokine sensitivity: F13a1 was down-regulated 3.3-fold by cytokines, Ripk2 was up-regulated 1.5- to 3-fold by all stressors, and Steap4 was profoundly cytokine sensitive (167-fold up-regulation). Three genes were thus closely associated with low-grade inflammation in murine islets and also with a marker for islet function (AIRg) in a diabetes-prone human population. This islet-targeted genome-wide association scan identified several previously unrecognized candidate genes related to islet dysfunction during the development of T2D.
Indexed as
Stress, PhysiologicalAnimalsCarrier ProteinsDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Factor XIIIGene Expression ProfilingGenome-Wide Association StudyHumansInflammationInterleukin-1betaInterleukin-6Islets of LangerhansMaleMembrane ProteinsMiceCarrier ProteinsFactor XIIIInterleukin-1betaInterleukin-6Klhl6 protein, mouseMembrane ProteinsPamr1 protein, mouseReceptor-Interacting Protein Serine-Threonine Kinase 2Receptor-Interacting Protein Serine-Threonine KinasesRipk2 protein, mouseSerine EndopeptidasesSerine ProteasesTiarp protein, mouse
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