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      Action of Phytochemicals on Insulin Signaling Pathways Accelerating Glucose Transporter (GLUT4) Protein Translocation

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          Abstract

          Diabetes is associated with obesity, generally accompanied by a chronic state of oxidative stress and redox imbalances which are implicated in the progression of micro- and macro-complications like heart disease, stroke, dementia, cancer, kidney failure and blindness. All these complications rise primarily due to consistent high blood glucose levels. Insulin and glucagon help to maintain the homeostasis of glucose and lipids through signaling cascades. Pancreatic hormones stimulate translocation of the glucose transporter isoform 4 (GLUT4) from an intracellular location to the cell surface and facilitate the rapid insulin-dependent storage of glucose in muscle and fat cells. Malfunction in glucose uptake mechanisms, primarily contribute to insulin resistance in type 2 diabetes. Plant secondary metabolites, commonly known as phytochemicals, are reported to have great benefits in the management of type 2 diabetes. The role of phytochemicals and their action on insulin signaling pathways through stimulation of GLUT4 translocation is crucial to understand the pathogenesis of this disease in the management process. This review will summarize the effects of phytochemicals and their action on insulin signaling pathways accelerating GLUT4 translocation based on the current literature.

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          Most cited references79

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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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            Major facilitator superfamily.

            The major facilitator superfamily (MFS) is one of the two largest families of membrane transporters found on Earth. It is present ubiquitously in bacteria, archaea, and eukarya and includes members that can function by solute uniport, solute/cation symport, solute/cation antiport and/or solute/solute antiport with inwardly and/or outwardly directed polarity. All homologous MFS protein sequences in the public databases as of January 1997 were identified on the basis of sequence similarity and shown to be homologous. Phylogenetic analyses revealed the occurrence of 17 distinct families within the MFS, each of which generally transports a single class of compounds. Compounds transported by MFS permeases include simple sugars, oligosaccharides, inositols, drugs, amino acids, nucleosides, organophosphate esters, Krebs cycle metabolites, and a large variety of organic and inorganic anions and cations. Protein members of some MFS families are found exclusively in bacteria or in eukaryotes, but others are found in bacteria, archaea, and eukaryotes. All permeases of the MFS possess either 12 or 14 putative or established transmembrane alpha-helical spanners, and evidence is presented substantiating the proposal that an internal tandem gene duplication event gave rise to a primordial MFS protein prior to divergence of the family members. All 17 families are shown to exhibit the common feature of a well-conserved motif present between transmembrane spanners 2 and 3. The analyses reported serve to characterize one of the largest and most diverse families of transport proteins found in living organisms.
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              Glucose transporters in the 21st Century.

              The ability to take up and metabolize glucose at the cellular level is a property shared by the vast majority of existing organisms. Most mammalian cells import glucose by a process of facilitative diffusion mediated by members of the Glut (SLC2A) family of membrane transport proteins. Fourteen Glut proteins are expressed in the human and they include transporters for substrates other than glucose, including fructose, myoinositol, and urate. The primary physiological substrates for at least half of the 14 Glut proteins are either uncertain or unknown. The well-established glucose transporter isoforms, Gluts 1-4, are known to have distinct regulatory and/or kinetic properties that reflect their specific roles in cellular and whole body glucose homeostasis. Separate review articles on many of the Glut proteins have recently appeared in this journal. Here, we provide a very brief summary of the known properties of the 14 Glut proteins and suggest some avenues of future investigation in this area.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                MDPI
                1420-3049
                28 January 2018
                February 2018
                : 23
                : 2
                : 258
                Affiliations
                [1 ]Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; sayem066@ 123456gmail.com
                [2 ]Department of Pharmacology and Therapeutics, School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, Lakeside Campus, 47500 Subang Jaya, Malaysia; hamedkarimian61@ 123456gmail.com (H.K.); AmeyaAshok.Hasamnis@ 123456taylors.edu.my (A.A.H.)
                [3 ]Clinical Skills, School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, Lakeside Campus, 47500 Subang Jaya, Malaysia; Narendiran.Krishnasamy@ 123456taylors.edu.my
                [4 ]Department of Pharmacy, Faculty of Sciences and Engineering, East West University, Dhaka-1212, Bangladesh; faiz@ 123456ewubd.edu
                Author notes
                Article
                molecules-23-00258
                10.3390/molecules23020258
                6017132
                29382104
                cf100f47-0f73-40ba-b04f-43c3fbb0ec7d
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 December 2017
                : 23 January 2018
                Categories
                Review

                insulin receptor,insulin signaling pathways,pi3k,aps,glut4 translocation,phytochemicals

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