T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways
Objective: Beyond the taste buds, sweet taste receptors (STRs; T1R2/T1R3) are also expressed on enteroendocrine cells, where they regulate gut peptide secretion but their regulatory function within the intestine is largely unknown. Methods: Using T1R2-knock out (KO) mice we evaluated the role of STR...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-11-01
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| Series: | Molecular Metabolism |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877818304988 |
| _version_ | 1818574335687786496 |
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| author | Kathleen Smith Elnaz Karimian Azari Traci E. LaMoia Tania Hussain Veronika Vargova Katalin Karolyi Paula P. Veldhuis Juan Pablo Arnoletti Sebastian G. de la Fuente Richard E. Pratley Timothy F. Osborne George A. Kyriazis |
| author_facet | Kathleen Smith Elnaz Karimian Azari Traci E. LaMoia Tania Hussain Veronika Vargova Katalin Karolyi Paula P. Veldhuis Juan Pablo Arnoletti Sebastian G. de la Fuente Richard E. Pratley Timothy F. Osborne George A. Kyriazis |
| author_sort | Kathleen Smith |
| collection | DOAJ |
| description | Objective: Beyond the taste buds, sweet taste receptors (STRs; T1R2/T1R3) are also expressed on enteroendocrine cells, where they regulate gut peptide secretion but their regulatory function within the intestine is largely unknown. Methods: Using T1R2-knock out (KO) mice we evaluated the role of STRs in the regulation of glucose absorption in vivo and in intact intestinal preparations ex vivo. Results: STR signaling enhances the rate of intestinal glucose absorption specifically in response to the ingestion of a glucose-rich meal. These effects were mediated specifically by the regulation of GLUT2 transporter trafficking to the apical membrane of enterocytes. GLUT2 translocation and glucose transport was dependent and specific to glucagon-like peptide 2 (GLP-2) secretion and subsequent intestinal neuronal activation. Finally, high-sucrose feeding in wild-type mice induced rapid downregulation of STRs in the gut, leading to reduced glucose absorption. Conclusions: Our studies demonstrate that STRs have evolved to modulate glucose absorption via the regulation of its transport and to prevent the development of exacerbated hyperglycemia due to the ingestion of high levels of sugars. Keywords: Glucose homeostasis, Sweet taste receptors, GLP-2, GLUT2, T1R2 |
| first_indexed | 2024-12-15T00:25:14Z |
| format | Article |
| id | doaj.art-b5f0a7377256460193c5a2ac2e6f68cf |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-15T00:25:14Z |
| publishDate | 2018-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-b5f0a7377256460193c5a2ac2e6f68cf2022-12-21T22:42:12ZengElsevierMolecular Metabolism2212-87782018-11-011798111T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathwaysKathleen Smith0Elnaz Karimian Azari1Traci E. LaMoia2Tania Hussain3Veronika Vargova4Katalin Karolyi5Paula P. Veldhuis6Juan Pablo Arnoletti7Sebastian G. de la Fuente8Richard E. Pratley9Timothy F. Osborne10George A. Kyriazis11Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USACenter for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USACenter for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USACenter for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USATranslational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL, USACenter for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USAInstitute for Surgical Advancement, Florida Hospital, Orlando, FL, USAInstitute for Surgical Advancement, Florida Hospital, Orlando, FL, USAInstitute for Surgical Advancement, Florida Hospital, Orlando, FL, USATranslational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL, USACenter for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USACenter for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA; Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL, USA; Department of Biological Chemistry and Pharmacology, College of Medicine, The Ohio State University, Columbus, OH, USA; Corresponding author. Department of Biological Chemistry and Pharmacology, College of Medicine, The Ohio State University, 460 W 12th Ave, Columbus, OH 43210, USA.Objective: Beyond the taste buds, sweet taste receptors (STRs; T1R2/T1R3) are also expressed on enteroendocrine cells, where they regulate gut peptide secretion but their regulatory function within the intestine is largely unknown. Methods: Using T1R2-knock out (KO) mice we evaluated the role of STRs in the regulation of glucose absorption in vivo and in intact intestinal preparations ex vivo. Results: STR signaling enhances the rate of intestinal glucose absorption specifically in response to the ingestion of a glucose-rich meal. These effects were mediated specifically by the regulation of GLUT2 transporter trafficking to the apical membrane of enterocytes. GLUT2 translocation and glucose transport was dependent and specific to glucagon-like peptide 2 (GLP-2) secretion and subsequent intestinal neuronal activation. Finally, high-sucrose feeding in wild-type mice induced rapid downregulation of STRs in the gut, leading to reduced glucose absorption. Conclusions: Our studies demonstrate that STRs have evolved to modulate glucose absorption via the regulation of its transport and to prevent the development of exacerbated hyperglycemia due to the ingestion of high levels of sugars. Keywords: Glucose homeostasis, Sweet taste receptors, GLP-2, GLUT2, T1R2http://www.sciencedirect.com/science/article/pii/S2212877818304988 |
| spellingShingle | Kathleen Smith Elnaz Karimian Azari Traci E. LaMoia Tania Hussain Veronika Vargova Katalin Karolyi Paula P. Veldhuis Juan Pablo Arnoletti Sebastian G. de la Fuente Richard E. Pratley Timothy F. Osborne George A. Kyriazis T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways Molecular Metabolism |
| title | T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways |
| title_full | T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways |
| title_fullStr | T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways |
| title_full_unstemmed | T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways |
| title_short | T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways |
| title_sort | t1r2 receptor mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways |
| url | http://www.sciencedirect.com/science/article/pii/S2212877818304988 |
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