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      Orally administered saccharide-sequestering nanocomplex to manage carbohydrate metabolism disorders

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          Abstract

          A safe polymer limits the absorption of a broad spectrum of saccharides in the gut to manage metabolic disorders.

          Abstract

          Excessive carbohydrate intake is linked to the growing prevalence of diabetes, nonalcoholic fatty liver disease (NAFLD), and obesity. α-Glucosidases inhibitor, the only Food and Drug Administration–approved drug for limiting the absorption of polysaccharides and disaccharides, is ineffective for monosaccharides. Here, we develop a boronic acid–containing polymer nanocomplex (Nano-Poly-BA), absorbing all saccharides into nanocomplex with the diol/boronic acid molar ratio far above 1, to prevent saccharides’ absorption in the gut. The orally administered Nano-Poly-BA is nonabsorbable and nontoxic. When tested against four kinds of carbohydrates and three real-world foods (coke, blueberry jam, and porridge), Nano-Poly-BA shows remarkable after-meal blood glucose reductions in wild-type, type 1, and type 2 diabetic mouse models. In a NAFLD mouse model induced by fructose, Nano-Poly-BA shows substantial reduction of hepatic lipogenesis. In short, the orally administered saccharide-sequestering polymer nanocomplex may help prediabetic, diabetic, overweight, and even healthy people to manage sugar intake.

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          Most cited references31

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          A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010

          The Lancet, 380(9859), 2224-2260
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            Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues.

            Mucus is a viscoelastic and adhesive gel that protects the lung airways, gastrointestinal (GI) tract, vagina, eye and other mucosal surfaces. Most foreign particulates, including conventional particle-based drug delivery systems, are efficiently trapped in human mucus layers by steric obstruction and/or adhesion. Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on anatomical location, thereby strongly limiting the duration of sustained drug delivery locally. A number of debilitating diseases could be treated more effectively and with fewer side effects if drugs and genes could be more efficiently delivered to the underlying mucosal tissues in a controlled manner. This review first describes the tenacious mucus barrier properties that have precluded the efficient penetration of therapeutic particles. It then reviews the design and development of new mucus-penetrating particles that may avoid rapid mucus clearance mechanisms, and thereby provide targeted or sustained drug delivery for localized therapies in mucosal tissues.
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              Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease.

              Currently, we are experiencing an epidemic of cardiorenal disease characterized by increasing rates of obesity, hypertension, the metabolic syndrome, type 2 diabetes, and kidney disease. Whereas excessive caloric intake and physical inactivity are likely important factors driving the obesity epidemic, it is important to consider additional mechanisms. We revisit an old hypothesis that sugar, particularly excessive fructose intake, has a critical role in the epidemic of cardiorenal disease. We also present evidence that the unique ability of fructose to induce an increase in uric acid may be a major mechanism by which fructose can cause cardiorenal disease. Finally, we suggest that high intakes of fructose in African Americans may explain their greater predisposition to develop cardiorenal disease, and we provide a list of testable predictions to evaluate this hypothesis.
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                Author and article information

                Journal
                Sci Adv
                Sci Adv
                SciAdv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                March 2021
                31 March 2021
                : 7
                : 14
                : eabf7311
                Affiliations
                [1 ]School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
                [2 ]Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
                Author notes
                [* ]Corresponding author. Email: zhangshiyi@ 123456sjtu.edu.cn
                Author information
                http://orcid.org/0000-0003-0277-9524
                http://orcid.org/0000-0001-5945-0063
                http://orcid.org/0000-0001-7719-9896
                http://orcid.org/0000-0002-9539-6081
                http://orcid.org/0000-0003-0585-9423
                http://orcid.org/0000-0002-9375-5992
                Article
                abf7311
                10.1126/sciadv.abf7311
                8011972
                33789906
                1c86359a-8cb8-4b7a-94d6-e0682594f070
                Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 16 November 2020
                : 11 February 2021
                Funding
                Funded by: doi http://dx.doi.org/10.13039/501100004921, Shanghai Jiao Tong University;
                Award ID: WF220408211
                Funded by: doi http://dx.doi.org/10.13039/501100004921, Shanghai Jiao Tong University;
                Award ID: YG2017MS18
                Categories
                Research Article
                Research Articles
                SciAdv r-articles
                Materials Science
                Applied Sciences and Engineering
                Applied Sciences and Engineering
                Custom metadata
                Kyle Solis

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