The roles of cell-cell and organ-organ crosstalk in the type 2 diabetes mellitus associated inflammatory microenvironment |
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| Affiliation: | 1. The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, PR China;2. Peking University Fifth School of Clinical Medicine, Beijing 100730, PR China;3. Department of Clinical Laboratory, the Seventh Medical Centre of Chinese PLA General Hospital, Beijing 100700, PR China;1. Genetics Division, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Iran;2. Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran;3. Department of Cellular and molecular, School of Biological Sciences, Islamic Azad University of Falavarjan, Iran;4. Biotechnology department of Fasa University of medical science, Fasa, Iran;5. Department of Biology, Faculty of Science, University Of Isfahan, Isfahan, Iran;6. Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran;7. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran;8. Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Iran;9. Department of Biological Science and Technology, Faculty of Nano and Bio Science and Technology, Persian Gulf University, Bushehr 75169, Iran;10. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA;1. Department of Pain Treatment, Tangdu Hospital, Air Force Military Medical University, Xi’an 710032, China;2. Department of General Surgery, The 75th Group Army Hospital, Dali 671000, China;3. Department of Stomatology, Shaanxi Provincial Hospital, Xi''an, Shaanxi 710038, China;4. Department of Anesthesiology, the 920 Hospital of Joint Logistic Support Force of Chinese PLA, Kunming, Yunnan, China;5. Department of Gynaecology and Obstetrics, The 75th Group Army Hospital, Dali 671000, China;6. Department of Anorectal Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China;7. Department of Intervention Therapy, The Second Affiliated Hospital, Shaanxi University of Traditional Chinese Medicine, Xianyang 712046, China;1. College of Medicine, University of Sharjah, Sharjah 27272, UAE;2. Blood and Vascular Biology Research Lab, Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur 610005, India;3. Dermatology Institute, Translational Research Institute, Academic Health Systems, Hamad Medical Corporation, PO Box 3050, Doha, Qatar;4. Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, UAE;1. Department of Physiological Sciences, University of Stellenbosch, Stellenbosch, South Africa;2. Department of Internal Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Campus, South Africa;3. African Cancer Institute (ACI), Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa;4. Cancer Care SA, Cape Gate and Panorama Oncology Centres, Cape Town, South Africa;1. Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China;2. Department of Laboratory Medicine, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China;3. Department of Laboratory Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China |
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| Abstract: | Type 2 diabetes mellitus (T2DM) is a classic metaflammatory disease, and the inflammatory states of the pancreatic islet and insulin target organs have been well confirmed. However, abundant evidence demonstrates that there are countless connections between these organs in the presence of a low degree of inflammation. In this review, we focus on cell-cell crosstalk among local cells in the islet and organ-organ crosstalk among insulin-related organs. In contrast to that in acute inflammation, macrophages are the dominant immune cells causing inflammation in the islets and insulin target organs in T2DM. In the inflammatory microenvironment (IME) of the islet, cell-cell crosstalk involving local macrophage polarization and proinflammatory cytokine production impair insulin secretion by β-cells. Furthermore, organ-organ crosstalk, including the gut-brain-pancreas axis and interactions among insulin-related organs during inflammation, reduces insulin sensitivity and induces endocrine dysfunction. Therefore, this crosstalk ultimately results in a cascade leading to β-cell dysfunction. These findings could have broad implications for therapies aimed at treating T2DM. |
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| Keywords: | Type 2 diabetes mellitus Islet β-cell dysfunction Metaflammation Inflammatory microenvironment |
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