دورية أكاديمية
The Iminosugar AMP-DNM Improves Satiety and Activates Brown Adipose Tissue Through GLP1.
| العنوان: | The Iminosugar AMP-DNM Improves Satiety and Activates Brown Adipose Tissue Through GLP1. |
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| المؤلفون: | Herrera Moro Chao D; Department of Medical Biochemistry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Laboratory of Endocrinology, Department of Endocrinology and Metabolism, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Wang Y; Division of Endocrinology and Einthoven Laboratory for Experimental Vascular Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands., Foppen E; Laboratory of Endocrinology, Department of Endocrinology and Metabolism, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Ottenhoff R; Department of Medical Biochemistry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., van Roomen C; Department of Medical Biochemistry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Parlevliet ET; Division of Endocrinology and Einthoven Laboratory for Experimental Vascular Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands., van Eijk M; Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden, the Netherlands., Verhoek M; Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden, the Netherlands., Boot R; Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden, the Netherlands., Marques AR; Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden, the Netherlands., Scheij S; Department of Medical Biochemistry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Mirzaian M; Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden, the Netherlands., Kooijman S; Division of Endocrinology and Einthoven Laboratory for Experimental Vascular Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands., Jansen K; Laboratory of Endocrinology, Department of Endocrinology and Metabolism, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Wang D; Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands.; Institute of Plant Protection, Chinese Academy of Agricultural Science, Beijing, China., Mergen C; Helmholtz Diabetes Center and German Center for Diabetes Research, Helmholtz Zentrum München, Neuherberg, Germany, and Division of Metabolic Diseases, Technische Universität München, Munich, Germany., Seeley RJ; Department of Surgery, University of Michigan, MI., Tschöp MH; Helmholtz Diabetes Center and German Center for Diabetes Research, Helmholtz Zentrum München, Neuherberg, Germany, and Division of Metabolic Diseases, Technische Universität München, Munich, Germany., Overkleeft H; Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden, the Netherlands., Rensen PCN; Division of Endocrinology and Einthoven Laboratory for Experimental Vascular Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands., Kalsbeek A; Laboratory of Endocrinology, Department of Endocrinology and Metabolism, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands., Aerts JMFG; Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden, the Netherlands j.m.f.g.aerts@lic.leidenuniv.nl., Yi CX; Laboratory of Endocrinology, Department of Endocrinology and Metabolism, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. |
| المصدر: | Diabetes [Diabetes] 2019 Dec; Vol. 68 (12), pp. 2223-2234. Date of Electronic Publication: 2019 Oct 02. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Alexandria, VA : American Diabetes Association Original Publication: [New York, American Diabetes Association] |
| مواضيع طبية MeSH: | 1-Deoxynojirimycin/*analogs & derivatives , Adamantane/*analogs & derivatives , Adipose Tissue, Brown/*drug effects , Glucagon-Like Peptide 1/*physiology , Satiation/*drug effects, 1-Deoxynojirimycin/pharmacology ; Adamantane/pharmacology ; Animals ; Brain/drug effects ; Brain/physiology ; Glucose/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/drug therapy ; Obesity/metabolism ; Rats ; Rats, Wistar ; Signal Transduction/drug effects |
| مستخلص: | Obesity is taking on worldwide epidemic proportions, yet effective pharmacological agents with long-term efficacy remain unavailable. Previously, we designed the iminosugar N-adamantine-methyloxypentyl-deoxynojirimycin (AMP-DNM), which potently improves glucose homeostasis by lowering excessive glycosphingolipids. Here we show that AMP-DNM promotes satiety and activates brown adipose tissue (BAT) in obese rodents. Moreover, we demonstrate that the mechanism mediating these favorable actions depends on oral, but not central, administration of AMP-DNM, which ultimately stimulates systemic glucagon-like peptide 1 (GLP1) secretion. We evidence an essential role of brain GLP1 receptors (GLP1r), as AMP-DNM fails to promote satiety and activate BAT in mice lacking the brain GLP1r as well as in mice treated intracerebroventricularly with GLP1r antagonist exendin-9. In conclusion, AMP-DNM markedly ameliorates metabolic abnormalities in obese rodents by restoring satiety and activating BAT through central GLP1r, while improving glucose homeostasis by mechanisms independent of central GLP1r. (© 2019 by the American Diabetes Association.) |
| المشرفين على المادة: | 0 (N-(5-adamantane-1-yl-methoxy-pentyl)deoxynojirimycin) 19130-96-2 (1-Deoxynojirimycin) 89750-14-1 (Glucagon-Like Peptide 1) IY9XDZ35W2 (Glucose) PJY633525U (Adamantane) |
| تواريخ الأحداث: | Date Created: 20191004 Date Completed: 20200316 Latest Revision: 20200316 |
| رمز التحديث: | 20240628 |
| DOI: | 10.2337/db19-0049 |
| PMID: | 31578192 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1939-327X |
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| DOI: | 10.2337/db19-0049 |