6
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Influence of glucosamine on the bioactivity of insulin delivered subcutaneously and in an oral nanodelivery system

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The aim of the work reported herein was to study the effect of glucosamine HCl (GlcN·HCl) on the bioactivity (BA) of insulin, administered via subcutaneous (SC) and oral routes, in adult male Sprague Dawley rats. The oral insulin delivery system (insulin–chitosan reverse micelle [IC-RM]) was prepared by solubilizing insulin–chitosan (13 kDa) polyelectrolyte complex in a RM system consisting of oleic acid, PEG-8 caprylic/capric glycerides, and polyglycerol-6-dioleate. The BA of insulin in vivo was evaluated by measuring blood glucose level using a blood glucose meter; the results revealed that the extent of hypoglycemic activity of SC insulin was GlcN·HCl dose dependent when they were administered simultaneously. A significant reduction in blood glucose levels ( P<0.05) was found for the insulin:GlcN·HCl at mass ratios of 1:10 and 1:20, whereas lower ratios (eg, 1:1 and 1:4) showed no significant reduction. Furthermore, enhancement of the action of SC insulin was achieved by oral administration of GlcN·HCl for 5 consecutive days prior to insulin injection ( P<0.05). For oral insulin administration via the IC-RM system, the presence of GlcN·HCl increased the hypoglycemic activity of insulin ( P<0.05). The relative BA were 6.7% and 5.4% in the presence and absence of GlcN·HCl (ie, the increase in the relative BA was approximately 23% due to incorporating GlcN·HCl in the IC-RM system), respectively. The aforementioned findings offer an opportunity to incorporate GlcN·HCl in oral insulin delivery systems in order to enhance a reduction in blood glucose levels.

          Related collections

          Most cited references 40

          • Record: found
          • Abstract: found
          • Article: not found

          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.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Inhibiting NF-κB activation by small molecules as a therapeutic strategy.

            Because nuclear factor-κB (NF-κB) is a ubiquitously expressed proinflammatory transcription factor that regulates the expression of over 500 genes involved in cellular transformation, survival, proliferation, invasion, angiogenesis, metastasis, and inflammation, the NF-κB signaling pathway has become a potential target for pharmacological intervention. A wide variety of agents can activate NF-κB through canonical and noncanonical pathways. Canonical pathway involves various steps including the phosphorylation, ubiquitination, and degradation of the inhibitor of NF-κB (IκBα), which leads to the nuclear translocation of the p50-p65 subunits of NF-κB followed by p65 phosphorylation, acetylation and methylation, DNA binding, and gene transcription. Thus, agents that can inhibit protein kinases, protein phosphatases, proteasomes, ubiquitination, acetylation, methylation, and DNA binding steps have been identified as NF-κB inhibitors. Because of the critical role of NF-κB in cancer and various chronic diseases, numerous inhibitors of NF-κB have been identified. In this review, however, we describe only small molecules that suppress NF-κB activation, and the mechanism by which they block this pathway. Copyright © 2010 Elsevier B.V. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance.

              Based on our previous finding that desensitization of the insulin-responsive glucose transport system (GTS) requires three components, glucose, insulin, and glutamine, we postulated that the routing of incoming glucose through the hexosamine biosynthesis pathway plays a key role in the development of insulin resistance in primary cultured adipocytes. Two approaches were used to test this hypothesis. First, we assessed whether glucose-induced desensitization of the GTS could be prevented by glutamine analogs that irreversibly inactivate glutamine-requiring enzymes, such as glutamine:fructose-6-phosphate amidotransferase (GFAT) the first and the rate-limiting enzyme in hexosamine biosynthesis. Both O-diazoacetyl-L-serine (azaserine) and 6-diazo-5-oxonorleucine inhibited desensitization in 18-h treated cells without affecting maximal insulin responsiveness in control cells. Moreover, close agreement was seen between the ability of azaserine to prevent desensitization of the GTS in intact adipocytes (70% inhibition, ED50 = 1.1 microM), its ability to inactivate GFAT in intact adipocytes (64% inhibition, ED50 = 1.0 microM) and its ability to inactivate GFAT activity in a cytosolic adipocyte preparation (ED50 = 1.3 microM). From these results we concluded that a glutamine amidotransferase is involved in the induction of insulin resistance. As a second approach, we determined whether glucosamine, an agent known to preferentially enter the hexosamine pathway at a point distal to enzymatic amidation by GFAT, could induce cellular insulin resistance. When adipocytes were exposed to various concentrations of glucosamine for 5 h, progressive desensitization of the GTS was observed (ED50 = 0.36 mM) that culminated in a 40-50% loss of insulin responsiveness. Moreover, we estimated that glucosamine is at least 40 times more potent than glucose in mediating desensitization, since glucosamine entered adipocytes at only one-quarter of the glucose uptake rate, yet induced desensitization at an extra-cellular dose 10 times lower than glucose. In addition, we found that glucosamine-induced desensitization did not require glutamine and was unaffected by azaserine treatment. Thus, we conclude that glucosamine enters the hexosamine-desensitization pathway at a point distal to GFAT amidation. Overall, these studies indicate that a unique metabolic pathway exists in adipocytes that mediates desensitization of the insulin-responsive GTS, and reveal that an early step in this pathway involves the conversion of fructose 6-phosphate to glucosamine 6-phosphate by the first and rate-limiting enzyme of the hexosamine pathway, glutamine:fructose-6-phosphate amidotransferase.
                Bookmark

                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2015
                19 November 2015
                : 9
                : 6167-6176
                Affiliations
                [1 ]The Jordanian Pharmaceutical Manufacturing Company (PLC), Naor, Jordan
                [2 ]Faculty of Engineering and Science, University of Greenwich, Medway Campus, Kent, UK
                [3 ]Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan
                Author notes
                Correspondence: Adnan A Badwan, The Jordanian Pharmaceutical, Manufacturing Company (PLC), PO Box 94, Naor 11710, Jordan, Tel +962 6 5727 207, Fax +962 6 5727 641, Email jpm@ 123456go.com.jo
                Article
                dddt-9-6167
                10.2147/DDDT.S91974
                4657806
                26640369
                © 2015 Al-Kurdi et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Comments

                Comment on this article