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Regulation of Systemic Glucose Homeostasis by T Helper Type 2 Cytokines
Yea Eun Kang, Hyun Jin Kim, Minho Shong
Diabetes Metab J. 2019;43(5):549-559.   Published online October 24, 2019
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  • 97 Download
  • 10 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   

Obesity results in an inflammatory microenvironment in adipose tissue, leading to the deterioration of tissue protective mechanisms. Although recent studies suggested the importance of type 2 immunity in an anti-inflammatory microenvironment in adipose tissue, the regulatory effects of T helper 2 (Th2) cytokines on systemic metabolic regulation are not fully understood. Recently, we identified the roles of the Th2 cytokine (interleukin 4 [IL-4] and IL-13)-induced adipokine, growth differentiation factor 15 (GDF15), in adipose tissue in regulating systemic glucose metabolism via signal transducer and activator of transcription 6 (STAT6) activation. Moreover, we showed that mitochondrial oxidative phosphorylation is required to maintain these macrophage-regulating autocrine and paracrine signaling pathways via Th2 cytokine-induced secretion of GDF15. In this review, we discuss how the type 2 immune response and Th2 cytokines regulate metabolism in adipose tissue. Specifically, we review the systemic regulatory roles of Th2 cytokines in metabolic disease and the role of mitochondria in maintenance of type 2 responses in adipose tissue homeostasis.


Citations to this article as recorded by  
  • Orchestration of the Adipose Tissue Immune Landscape by Adipocytes
    David Bradley, Tuo Deng, Dharti Shantaram, Willa A. Hsueh
    Annual Review of Physiology.2024; 86(1): 199.     CrossRef
  • Growth and differentiation factor-15: A link between inflammaging and cardiovascular disease
    Balázs Bence Nyárády, Loretta Zsuzsa Kiss, Zsolt Bagyura, Béla Merkely, Edit Dósa, Orsolya Láng, László Kőhidai, Éva Pállinger
    Biomedicine & Pharmacotherapy.2024; 174: 116475.     CrossRef
  • Evaluation of Mitochondrial Function in Blood Samples Shows Distinct Patterns in Subjects with Thyroid Carcinoma from Those with Hyperplasia
    Julia Bernal-Tirapo, María Teresa Bayo Jiménez, Pedro Yuste-García, Isabel Cordova, Ana Peñas, Francisco-Javier García-Borda, Cesar Quintela, Ignacio Prieto, Cristina Sánchez-Ramos, Eduardo Ferrero-Herrero, María Monsalve
    International Journal of Molecular Sciences.2023; 24(7): 6453.     CrossRef
  • A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome
    Ronit Vogt Sionov, Ronit Ahdut-HaCohen
    Biomedicines.2023; 11(9): 2558.     CrossRef
  • Gdf15 deletion exacerbates acute lung injuries induced by intratracheal inoculation of aerosolized ricin in mice
    Mengyun Deng, Duo Su, Nan Xiao, Zhipeng Zhang, Yifeng Wang, Fuliang Zong, Sha Li, Jinglin Wang, Dongsheng Zhou, Yuee Zhao, Huiying Yang
    Toxicology.2022; 469: 153135.     CrossRef
  • Role of PPAR Receptor and Ligands in the Pathogenesis and Therapy of Hematologic Malignancies
    Jian Wu, Min Zhang, Allison Faircloth
    Hemato.2022; 3(3): 422.     CrossRef
  • Macrophage and Adipocyte Mitochondrial Dysfunction in Obesity-Induced Metabolic Diseases
    Liwen Wang, Jie Hu, Haiyan Zhou
    The World Journal of Men's Health.2021; 39(4): 606.     CrossRef
  • Th2 Cytokines Increase the Expression of Fibroblast Growth Factor 21 in the Liver
    Seul-Gi Kang, Seong-Eun Lee, Min-Jeong Choi, Joon-Young Chang, Jung-Tae Kim, Ben-Yuan Zhang, Yea-Eun Kang, Ju-Hee Lee, Hyon-Seung Yi, Minho Shong
    Cells.2021; 10(6): 1298.     CrossRef
  • Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint
    Jörg Wischhusen, Ignacio Melero, Wolf Herman Fridman
    Frontiers in Immunology.2020;[Epub]     CrossRef
  • Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages
    Irina Larionova, Elena Kazakova, Marina Patysheva, Julia Kzhyshkowska
    Cancers.2020; 12(6): 1411.     CrossRef
Double Diabetes.
Sang Youl Rhee, Young Seol Kim
Korean Diabetes J. 2009;33(1):1-8.   Published online February 1, 2009
  • 2,078 View
  • 26 Download
AbstractAbstract PDF
Generally, most cases of diabetes mellitus (DM) are classified as either type 1 DM or type 2 DM based on their pathophysiolgic features. However, it is not always possible to classify this disease clearly according to current diagnostic criteria. Recently, the existence of non-typical diabetes has been found in patients with simultaneous features of both type 1 and type 2 DM. In these patients, obvious evidence of insulin resistance, positivity of islet autoantibody, and progressive beta cell loss are observed concurrently. Moreover, this non-typical diabetes that usually occurs among children and adolescents has been defined as 'double diabetes', and its worldwide incidence has been on the increase as of late. Thus, there has been heightened interest among researchers about this ambiguous condition.
Original Article
Five Year Follow-up of ICA and GADA in Childhood onset Type 1 DM.
Si Hyung Lee, Ji Sung Yoon, Mi Jung Eun, Jin Ho Kim, Yong Ho Park, Kyu Chang Won, Ihn Ho Jo, Hyoung Woo Lee
Korean Diabetes J. 2003;27(5):395-404.   Published online October 1, 2003
  • 1,243 View
  • 19 Download
AbstractAbstract PDF
Type 1 diabetes develops due to the destruction of insulin-secreting beta-cells by an autoimmune process, in which both genetic and environmental factors are involved. In children with newly diagnosed type 1 DM, the prevalence of ICA (Islet cell cytoplasmic antibody) is 60~86% and is highest at the time of onset after which it decreases. But, GADA (glutamic acid decarboxylase anti- bodies) are characterized by substantial fluctuations in the humoral immune response over a long period after clinical manifestation. This study was performed to evaluate the persistence of type 1 DM associated autoantibodies, including ICA and GADA, and their relation to clinical characteristics of the disease after clinical manifestation. METHODS: Eighteen childhood onset type 1 diabetes patients (mean age 13.7 years; duration 3.9 years) were included in this study. ICA was measured by indirect immunofluorescence using conventional ICA-IgG and positive samples were titered by serial dilutions. Also the sera were screened for GADA by radioimmuno-assay. RESULTS: The positivities of ICA and GADA at the time of study were 55.6% and 61%, falling to 44.4% and 41.2% 5 years later, respectively. There was no case of an ICA negative patient becoming positive or whose ICA titer was increased later. One case of a GADA negative patient became positive later. Initial c-peptide levels didn't have any correlation with initial ICA titers or ICA prevalence, but did with initial GADA titer. There were significant correlations between initial GADA titer and ICA prevalence (p<0.001), and between initial GADA titer or ICA titer and later ICA persistence (p<0.05). CONCLUSION: ICA and GADA persisted long after the clinical diagnosis of type 1 diabetes. And the persistence of autoantibody positivity showed a weak relation with endogenous insulin secretion and clinical characteristics, both at and after diagnosis of overt type 1 diabetes.

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