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      Serum from Jiao-Tai-Wan treated rats increases glucose consumption by 3T3-L1 adipocytes through AMPK pathway signaling

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          Abstract

          Type 2 diabetes (T2DM) is characterized by hyperglycemia resulting from insulin resistance. Jiao-Tai-Wan (JTW), a traditional Chinese medicine consisting of a 10:1 formulation of Rhizoma Coptidis (RC) and Cortex Cinnamomi (cinnamon) was shown to have hypoglycemic efficacy in a type 2 diabetic mouse model. Here we investigated whether glucose consumption by insulin-resistant adipocytes could be modulated by serum from JTW-treated rats, and if so, through what mechanism. JTW-medicated serum was prepared from rats following oral administration of JTW decoction twice a day for 4 days. Fully differentiated 3T3-L1 adipocytes – rendered insulin resistance by dexamethasone treatment – were cultured in medium containing JTW-medicated rat serum. JTW-medicated serum treatment increased glucose uptake, up-regulated levels of phosphorylated adenosine 5′-monophoshate-activated protein kinase (p-AMPK), and stimulated expression and translocation of glucose transporter 4 (GLUT4). JTW-medicated serum induced significantly greater up-regulation of p-AMPK and GLUT4 than either RC or cinnamon-medicated serum. JTW-medicated serum induced effects on 3T3-L1 adipocytes could be partially inhibited by treatment with the AMPK inhibitor compound C. In conclusion, JTW-medicated serum increased glucose consumption by IR adipocytes partially through the activation of the AMPK pathway, and JTW was more effective on glucose consumption than either RC or cinnamon alone.

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          Most cited references19

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          The SLC2 (GLUT) family of membrane transporters.

          GLUT proteins are encoded by the SLC2 genes and are members of the major facilitator superfamily of membrane transporters. Fourteen GLUT proteins are expressed in the human and they are categorized into three classes based on sequence similarity. All GLUTs appear to transport hexoses or polyols when expressed ectopically, but the primary physiological substrates for several of the GLUTs remain uncertain. GLUTs 1-5 are the most thoroughly studied and all have well established roles as glucose and/or fructose transporters in various tissues and cell types. The GLUT proteins are comprised of ∼500 amino acid residues, possess a single N-linked oligosaccharide, and have 12 membrane-spanning domains. In this review we briefly describe the major characteristics of the 14 GLUT family members. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Targeting adipose tissue in the treatment of obesity-associated diabetes

            Adipose tissue regulates numerous physiological processes, and its dysfunction in obese humans is associated with disrupted metabolic homeostasis, insulin resistance and type 2 diabetes mellitus (T2DM). Although several US-approved treatments for obesity and T2DM exist, these are limited by adverse effects and a lack of effective long-term glucose control. In this Review, we provide an overview of the role of adipose tissue in metabolic homeostasis and assess emerging novel therapeutic strategies targeting adipose tissue, including adipokine-based strategies, promotion of white adipose tissue beiging as well as reduction of inflammation and fibrosis.
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              Selective Impairment of Glucose but Not Fatty Acid or Oxidative Metabolism in Brown Adipose Tissue of Subjects With Type 2 Diabetes.

              Spontaneous glucose uptake by brown adipose tissue (BAT) is lower in overweight or obese individuals and in diabetes. However, BAT metabolism has not been previously investigated in patients with type 2 diabetes during controlled cold exposure. Using positron emission tomography with (11)C-acetate, (18)F-fluoro-deoxyglucose ((18)FDG), and (18)F-fluoro-thiaheptadecanoic acid ((18)FTHA), a fatty acid tracer, BAT oxidative metabolism and perfusion and glucose and nonesterified fatty acid (NEFA) turnover were determined in men with well-controlled type 2 diabetes and age-matched control subjects under experimental cold exposure designed to minimize shivering. Despite smaller volumes of (18)FDG-positive BAT and lower glucose uptake per volume of BAT compared with young healthy control subjects, cold-induced oxidative metabolism and NEFA uptake per BAT volume and an increase in total body energy expenditure did not differ in patients with type 2 diabetes or their age-matched control subjects. The reduction in (18)FDG-positive BAT volume and BAT glucose clearance were associated with a reduction in BAT radiodensity and perfusion. (18)FDG-positive BAT volume and the cold-induced increase in BAT radiodensity were associated with an increase in systemic NEFA turnover. These results show that cold-induced NEFA uptake and oxidative metabolism are not defective in type 2 diabetes despite reduced glucose uptake per BAT volume and BAT "whitening."
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                Author and article information

                Journal
                Biosci Rep
                Biosci. Rep
                ppbioscirep
                BSR
                Bioscience Reports
                Portland Press Ltd.
                0144-8463
                1573-4935
                18 March 2019
                30 April 2019
                05 April 2019
                : 39
                : 4
                : BSR20181286
                Affiliations
                Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
                Author notes
                Correspondence: Xiong Lu ( xionglu93@ 123456126.com )
                [*]

                These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0002-5853-9637
                Article
                10.1042/BSR20181286
                6449522
                30886061
                da2079a0-8889-4be6-af86-d49e62dae089
                © 2019 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                : 28 July 2018
                : 05 March 2019
                : 14 March 2019
                Page count
                Pages: 10
                Categories
                Research Articles
                Research Article
                10
                13
                41

                Life sciences
                ampk,glucose uptake,glut4,insulin resistance,jiao-tai-wan decoction
                Life sciences
                ampk, glucose uptake, glut4, insulin resistance, jiao-tai-wan decoction

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