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      Insulin resistance: Review of the underlying molecular mechanisms

      1 , 1 , 2 , 3 , 4 , 5
      Journal of Cellular Physiology
      Wiley

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          Abstract

          Most human cells utilize glucose as the primary substrate, cellular uptake requiring insulin. Insulin signaling is therefore critical for these tissues. However, decrease in insulin sensitivity due to the disruption of various molecular pathways causes insulin resistance (IR). IR underpins many metabolic disorders such as type 2 diabetes and metabolic syndrome, impairments in insulin signaling disrupting entry of glucose into the adipocytes, and skeletal muscle cells. Although the exact underlying cause of IR has not been fully elucidated, a number of major mechanisms, including oxidative stress, inflammation, insulin receptor mutations, endoplasmic reticulum stress, and mitochondrial dysfunction have been suggested. In this review, we consider the role these cellular mechanisms play in the development of IR.

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          Most cited references52

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          IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040.

          To produce current estimates of the national, regional and global impact of diabetes for 2015 and 2040.
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            Adipose tissue, adipokines, and inflammation.

            White adipose tissue is no longer considered an inert tissue mainly devoted to energy storage but is emerging as an active participant in regulating physiologic and pathologic processes, including immunity and inflammation. Macrophages are components of adipose tissue and actively participate in its activities. Furthermore, cross-talk between lymphocytes and adipocytes can lead to immune regulation. Adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, including the adipokines leptin, adiponectin, resistin, and visfatin, as well as cytokines and chemokines, such as TNF-alpha, IL-6, monocyte chemoattractant protein 1, and others. Proinflammatory molecules produced by adipose tissue have been implicated as active participants in the development of insulin resistance and the increased risk of cardiovascular disease associated with obesity. In contrast, reduced leptin levels might predispose to increased susceptibility to infection caused by reduced T-cell responses in malnourished individuals. Altered adipokine levels have been observed in a variety of inflammatory conditions, although their pathogenic role has not been completely clarified.
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              Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future.

              Glucose metabolism is normally regulated by a feedback loop including islet β cells and insulin-sensitive tissues, in which tissue sensitivity to insulin affects magnitude of β-cell response. If insulin resistance is present, β cells maintain normal glucose tolerance by increasing insulin output. Only when β cells cannot release sufficient insulin in the presence of insulin resistance do glucose concentrations rise. Although β-cell dysfunction has a clear genetic component, environmental changes play an essential part. Modern research approaches have helped to establish the important role that hexoses, aminoacids, and fatty acids have in insulin resistance and β-cell dysfunction, and the potential role of changes in the microbiome. Several new approaches for treatment have been developed, but more effective therapies to slow progressive loss of β-cell function are needed. Recent findings from clinical trials provide important information about methods to prevent and treat type 2 diabetes and some of the adverse effects of these interventions. However, additional long-term studies of drugs and bariatric surgery are needed to identify new ways to prevent and treat type 2 diabetes and thereby reduce the harmful effects of this disease. Copyright © 2014 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Journal of Cellular Physiology
                J Cell Physiol
                Wiley
                0021-9541
                1097-4652
                November 27 2018
                June 2019
                October 14 2018
                June 2019
                : 234
                : 6
                : 8152-8161
                Affiliations
                [1 ]Chronic Kidney Disease Research Center, Shahid Beheshti University of Medical SciencesTehran Iran
                [2 ]Diabetes Research Center, Qatar Biomedical Research InstituteDoha Qatar
                [3 ]Neurogenic Inflammation Research Center, Mashhad University of Medical SciencesMashhad Iran
                [4 ]Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesMashhad Iran
                [5 ]School of Pharmacy, Mashhad University of Medical SciencesMashhad Iran
                Article
                10.1002/jcp.27603
                30317615
                0d25f440-38af-4cbe-843a-2ccf1c156333
                © 2019

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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