Role of the DNAJ/HSP40 family in the pathogenesis of insulin resistance and type 2 diabetes |
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| Institution: | 1. School of Life Sciences, University of Science and Technology of China, Hefei, 230026, China;2. Hefei National Laboratory for Physical Sciences at the Microscale, Division of Molecular and Cellular Biophysics, University of Science and Technology of China, Hefei, 230026, China;3. Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, China;1. Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456, Coimbra, Portugal;2. CNC - Center for Neuroscience and Cell Biology, CIBB, 3004-504, Coimbra, Portugal;1. Department of Environmental Health Sciences, Morrill I, N344, University of Massachusetts, Amherst, MA, 01003, USA;2. Department of Biomedical and Biotechnological Sciences, School of Medicine University of Catania, Via Santa Sofia 78, Catania, 95123, Italy;3. Departments of Neurology and Biochemistry, Georgetown University Medical Center, Washington, DC, 20057, USA;1. Department of Medicine III & Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany;2. Department of Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT, USA;3. Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA;1. Primary Care Department, USL Toscana Sud Est-Grosseto, Grosseto, Italy;2. Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy;3. Division of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy;4. Immunohaematology and Transfusion Medicine Service, USL Toscana Nord Ovest, San Luca Hospital, Lucca, Italy;5. Cardiology Unit, USL Toscana Sus Est Grosseto, Grosseto, Italy;6. Department of Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, Canada;7. Departments of Oncology and Community Health Sciences, University of Calgary, Calgary, Canada;8. Department of Geriatric Medicine, Bezmialem Vakif University, Faculty of Medicine, Istanbul, Turkey;9. Vision and Eye Research Institute, School of Medicine, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University-Cambridge Campus, Cambridge, United Kingdom;10. Department of Social and Preventive Medicine, Centre for Public Health, Medical University of Vienna, Austria;11. The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, United Kingdom;12. Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova, Padova, Italy;13. Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy;14. Geriatric Unit, Department of Internal Medicine and Geriatrics, University of Palermo, Palermo, Italy;1. Immunosenescence Study Group, Department of Biomedicine, Neuroscience and Advanced, Diagnostics (Bi.N.D.), University of Palermo, Palermo, Italy;2. Cellular/Molecular Biology and Clinical Pathology Laboratory, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, Palermo, Italy |
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| Abstract: | Insulin resistance (IR) underpins a wide range of metabolic disorders including type 2 diabetes (T2D), metabolic syndrome and cardiovascular diseases. IR is characterized by a marked reduction in the magnitude and/or delayed onset of insulin to stimulate glucose disposal. This condition is due to defects in one or several intracellular intermediates of the insulin signaling cascade, ranging from insulin receptor substrate (IRS) inactivation to reduced glucose phosphorylation and oxidation. Genetic predisposition, as well as other precipitating factors such as aging, obesity, and sedentary lifestyles are among the risk factors underlying the pathogenesis of IR and its subsequent progression to T2D. One of the cardinal hallmarks of T2D is the impairment of the heat shock response (HSR). Human and animal studies provided compelling evidence of reduced expression of several components of the HSR (i.e. Heat shock proteins or HSPs) in diabetic samples in a manner that correlates with the degree of IR. Interventions that induce the HSR, irrespective of the means to achieve it, proved their effectiveness in enhancing insulin sensitivity and improving glycemic index. However, most of these studies have been focused on HSP70 family. In this review, we will focus on the novel role of DNAJ/HSP40 cochaperone family in metabolic diseases associated with IR. |
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| Keywords: | Insulin resistance Type 2 diabetes Heat shock proteins Molecular chaperones Metabolic stress β-cell function |
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