Pine bark extract inhibits glucose transport in enterocytes via mitogen-activated kinase and phosphoinositol 3-kinase
Abstract Objective Pine bark extract (PBE) has been reported to have hypoglycemic effects but its mode of action is still unclear. This work studied the effect of PBE on glucose uptake by Caco-2 cells in isolation of its effect on insulin, which may appear if ingested by the animal. Methods Caco-2 c...
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| Veröffentlicht in: | Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2011-06, Vol.27 (6), p.707-712 |
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| creator | El-Zein, Ola, M.Sc Kreydiyyeh, Sawsan Ibrahim, Ph.D |
| description | Abstract Objective Pine bark extract (PBE) has been reported to have hypoglycemic effects but its mode of action is still unclear. This work studied the effect of PBE on glucose uptake by Caco-2 cells in isolation of its effect on insulin, which may appear if ingested by the animal. Methods Caco-2 cells were incubated in the presence of PBE and [14 C] 3-O-methyl-D-glucose as a tracer and the change in radioactivity of the incubation medium was taken as a measurement of glucose uptake. To determine the mechanism of action of the extract and type of transporters involved, Na+ -coupled glucose transporter-1 (SGLT1) and glucose transporter-2 (GLUT2) and different signaling mediators known to be involved in glucose transport were inactivated by specific inhibitors. Changes in the protein expression of glucose transporters were studied by western blotting. Results The extract significantly decreased glucose transport but did not affect the activity or expression of Na+ /K+ adenosine triphosphatase. It was concluded that PBE affects the number of glucose transporters in the brush-border membrane. This conclusion was confirmed by western blot analysis. The results showed that the extract acts by activating p38 mitogen-activated kinase, which in turn activates SGLT1 transporters and two different pathways that target GLUT2: an inhibitory pathway involving phosphoinositol 3-kinase and a stimulatory pathway involving mitogen activated protein kinase/extracellular signal-regulated kinase kinase. The activity of the two pathways is orchestrated by SGLT1. Conclusion Pine bark extract inhibits glucose absorption by p38 mitogen-activated kinase and constitutes a potential complementary therapeutic or prophylactic agent for diabetes and its complications. |
| doi_str_mv | 10.1016/j.nut.2010.07.001 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_865695887</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0899900710002261</els_id><sourcerecordid>865695887</sourcerecordid><originalsourceid>FETCH-LOGICAL-c465t-91f36c351e90afd89c8ab7469b25988d217338e34fcacd8cb56444f1a986d56e3</originalsourceid><addsrcrecordid>eNp9kk2LFDEQhoMo7jr6A7xIQMRTj_nqdIIgyOIXLCio55BOV-9mpicZk_Tg_HvTzOjCHjyEkNTzVipvFULPKVlTQuWbzTrMZc1IPZNuTQh9gC6p6nhDmRAP0SVRWjeakO4CPcl5QyqhpX6MLhhRUjPCL9H8zQfAvU1bDL9Lsq5gH25970vGN9PsYgZcr0Pex7SEMIQCKbpjgYwP3uKdL_EGQlOV_mALDHjrg60qGwa8v425Lh9irtiEeXMKPkWPRjtleHbeV-jnxw8_rj43118_fbl6f904IdvSaDpy6XhLQRM7Dko7ZftOSN2zVis1MNpxroCL0Vk3KNe3UggxUquVHFoJfIVen_LuU_w1Qy5m57ODabIB4pyNkq3UraqWrdDLe-QmzinU4gylnDAlOq0rRU-USzHnBKPZJ7-z6WgoMUtLzMbUlpilJYZ0phpeNS_Omed-B8M_xd8eVODVGbDZ2Wmsbjuf7zhBJRN8SfT2xEF17OAhmew8BAeDT-CKGaL_bxnv7qnd5IOvD27hCPnutyYzQ8z3ZXaW0aF1ahiTlP8BYPC_Sg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1130284799</pqid></control><display><type>article</type><title>Pine bark extract inhibits glucose transport in enterocytes via mitogen-activated kinase and phosphoinositol 3-kinase</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><source>ProQuest Central UK/Ireland</source><creator>El-Zein, Ola, M.Sc ; Kreydiyyeh, Sawsan Ibrahim, Ph.D</creator><creatorcontrib>El-Zein, Ola, M.Sc ; Kreydiyyeh, Sawsan Ibrahim, Ph.D</creatorcontrib><description>Abstract Objective Pine bark extract (PBE) has been reported to have hypoglycemic effects but its mode of action is still unclear. This work studied the effect of PBE on glucose uptake by Caco-2 cells in isolation of its effect on insulin, which may appear if ingested by the animal. Methods Caco-2 cells were incubated in the presence of PBE and [14 C] 3-O-methyl-D-glucose as a tracer and the change in radioactivity of the incubation medium was taken as a measurement of glucose uptake. To determine the mechanism of action of the extract and type of transporters involved, Na+ -coupled glucose transporter-1 (SGLT1) and glucose transporter-2 (GLUT2) and different signaling mediators known to be involved in glucose transport were inactivated by specific inhibitors. Changes in the protein expression of glucose transporters were studied by western blotting. Results The extract significantly decreased glucose transport but did not affect the activity or expression of Na+ /K+ adenosine triphosphatase. It was concluded that PBE affects the number of glucose transporters in the brush-border membrane. This conclusion was confirmed by western blot analysis. The results showed that the extract acts by activating p38 mitogen-activated kinase, which in turn activates SGLT1 transporters and two different pathways that target GLUT2: an inhibitory pathway involving phosphoinositol 3-kinase and a stimulatory pathway involving mitogen activated protein kinase/extracellular signal-regulated kinase kinase. The activity of the two pathways is orchestrated by SGLT1. Conclusion Pine bark extract inhibits glucose absorption by p38 mitogen-activated kinase and constitutes a potential complementary therapeutic or prophylactic agent for diabetes and its complications.</description><identifier>ISSN: 0899-9007</identifier><identifier>EISSN: 1873-1244</identifier><identifier>DOI: 10.1016/j.nut.2010.07.001</identifier><identifier>PMID: 20869203</identifier><identifier>CODEN: NUTRER</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Bark ; Biological and medical sciences ; Biological Transport - drug effects ; Caco-2 Cells ; Diabetes ; Diabetes Mellitus - drug therapy ; Enterocytes ; Enterocytes - drug effects ; Enterocytes - metabolism ; Enzyme Inhibitors - pharmacology ; Feeding. Feeding behavior ; Fundamental and applied biological sciences. Psychology ; Gastroenterology and Hepatology ; Glucose ; Glucose - metabolism ; Glucose Transporter Type 2 - antagonists & inhibitors ; Glucose Transporter Type 2 - metabolism ; Glucose transporter-2 ; Humans ; Hypoglycemic Agents - pharmacology ; Insulin ; Intestinal Absorption - drug effects ; Kinases ; MAP Kinase Signaling System - drug effects ; Membrane Transport Modulators - pharmacology ; Mitogen activated protein kinase/extracellular signal-regulated kinase kinase ; Mode of action ; Na +-coupled glucose transport ; p38 Mitogen-activated kinase ; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases - metabolism ; Phosphatidylinositol 3-Kinase - antagonists & inhibitors ; Phosphatidylinositol 3-Kinase - metabolism ; Phosphoinositol 3-kinase ; Phytotherapy ; Pine bark extract ; Pinus - chemistry ; Plant Bark - chemistry ; Plant extracts ; Plant Extracts - pharmacology ; Proteins ; Radioactivity ; Sodium-Glucose Transporter 1 - antagonists & inhibitors ; Sodium-Glucose Transporter 1 - metabolism ; Sodium-Potassium-Exchanging ATPase - metabolism ; Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><ispartof>Nutrition (Burbank, Los Angeles County, Calif.), 2011-06, Vol.27 (6), p.707-712</ispartof><rights>Elsevier Inc.</rights><rights>2011 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-91f36c351e90afd89c8ab7469b25988d217338e34fcacd8cb56444f1a986d56e3</citedby><cites>FETCH-LOGICAL-c465t-91f36c351e90afd89c8ab7469b25988d217338e34fcacd8cb56444f1a986d56e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1130284799?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24162431$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20869203$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>El-Zein, Ola, M.Sc</creatorcontrib><creatorcontrib>Kreydiyyeh, Sawsan Ibrahim, Ph.D</creatorcontrib><title>Pine bark extract inhibits glucose transport in enterocytes via mitogen-activated kinase and phosphoinositol 3-kinase</title><title>Nutrition (Burbank, Los Angeles County, Calif.)</title><addtitle>Nutrition</addtitle><description>Abstract Objective Pine bark extract (PBE) has been reported to have hypoglycemic effects but its mode of action is still unclear. This work studied the effect of PBE on glucose uptake by Caco-2 cells in isolation of its effect on insulin, which may appear if ingested by the animal. Methods Caco-2 cells were incubated in the presence of PBE and [14 C] 3-O-methyl-D-glucose as a tracer and the change in radioactivity of the incubation medium was taken as a measurement of glucose uptake. To determine the mechanism of action of the extract and type of transporters involved, Na+ -coupled glucose transporter-1 (SGLT1) and glucose transporter-2 (GLUT2) and different signaling mediators known to be involved in glucose transport were inactivated by specific inhibitors. Changes in the protein expression of glucose transporters were studied by western blotting. Results The extract significantly decreased glucose transport but did not affect the activity or expression of Na+ /K+ adenosine triphosphatase. It was concluded that PBE affects the number of glucose transporters in the brush-border membrane. This conclusion was confirmed by western blot analysis. The results showed that the extract acts by activating p38 mitogen-activated kinase, which in turn activates SGLT1 transporters and two different pathways that target GLUT2: an inhibitory pathway involving phosphoinositol 3-kinase and a stimulatory pathway involving mitogen activated protein kinase/extracellular signal-regulated kinase kinase. The activity of the two pathways is orchestrated by SGLT1. Conclusion Pine bark extract inhibits glucose absorption by p38 mitogen-activated kinase and constitutes a potential complementary therapeutic or prophylactic agent for diabetes and its complications.</description><subject>Bark</subject><subject>Biological and medical sciences</subject><subject>Biological Transport - drug effects</subject><subject>Caco-2 Cells</subject><subject>Diabetes</subject><subject>Diabetes Mellitus - drug therapy</subject><subject>Enterocytes</subject><subject>Enterocytes - drug effects</subject><subject>Enterocytes - metabolism</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Feeding. Feeding behavior</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastroenterology and Hepatology</subject><subject>Glucose</subject><subject>Glucose - metabolism</subject><subject>Glucose Transporter Type 2 - antagonists & inhibitors</subject><subject>Glucose Transporter Type 2 - metabolism</subject><subject>Glucose transporter-2</subject><subject>Humans</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Insulin</subject><subject>Intestinal Absorption - drug effects</subject><subject>Kinases</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Membrane Transport Modulators - pharmacology</subject><subject>Mitogen activated protein kinase/extracellular signal-regulated kinase kinase</subject><subject>Mode of action</subject><subject>Na +-coupled glucose transport</subject><subject>p38 Mitogen-activated kinase</subject><subject>p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Phosphatidylinositol 3-Kinase - antagonists & inhibitors</subject><subject>Phosphatidylinositol 3-Kinase - metabolism</subject><subject>Phosphoinositol 3-kinase</subject><subject>Phytotherapy</subject><subject>Pine bark extract</subject><subject>Pinus - chemistry</subject><subject>Plant Bark - chemistry</subject><subject>Plant extracts</subject><subject>Plant Extracts - pharmacology</subject><subject>Proteins</subject><subject>Radioactivity</subject><subject>Sodium-Glucose Transporter 1 - antagonists & inhibitors</subject><subject>Sodium-Glucose Transporter 1 - metabolism</subject><subject>Sodium-Potassium-Exchanging ATPase - metabolism</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><issn>0899-9007</issn><issn>1873-1244</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kk2LFDEQhoMo7jr6A7xIQMRTj_nqdIIgyOIXLCio55BOV-9mpicZk_Tg_HvTzOjCHjyEkNTzVipvFULPKVlTQuWbzTrMZc1IPZNuTQh9gC6p6nhDmRAP0SVRWjeakO4CPcl5QyqhpX6MLhhRUjPCL9H8zQfAvU1bDL9Lsq5gH25970vGN9PsYgZcr0Pex7SEMIQCKbpjgYwP3uKdL_EGQlOV_mALDHjrg60qGwa8v425Lh9irtiEeXMKPkWPRjtleHbeV-jnxw8_rj43118_fbl6f904IdvSaDpy6XhLQRM7Dko7ZftOSN2zVis1MNpxroCL0Vk3KNe3UggxUquVHFoJfIVen_LuU_w1Qy5m57ODabIB4pyNkq3UraqWrdDLe-QmzinU4gylnDAlOq0rRU-USzHnBKPZJ7-z6WgoMUtLzMbUlpilJYZ0phpeNS_Omed-B8M_xd8eVODVGbDZ2Wmsbjuf7zhBJRN8SfT2xEF17OAhmew8BAeDT-CKGaL_bxnv7qnd5IOvD27hCPnutyYzQ8z3ZXaW0aF1ahiTlP8BYPC_Sg</recordid><startdate>20110601</startdate><enddate>20110601</enddate><creator>El-Zein, Ola, M.Sc</creator><creator>Kreydiyyeh, Sawsan Ibrahim, Ph.D</creator><general>Elsevier Inc</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RQ</scope><scope>7RV</scope><scope>7TS</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20110601</creationdate><title>Pine bark extract inhibits glucose transport in enterocytes via mitogen-activated kinase and phosphoinositol 3-kinase</title><author>El-Zein, Ola, M.Sc ; Kreydiyyeh, Sawsan Ibrahim, Ph.D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-91f36c351e90afd89c8ab7469b25988d217338e34fcacd8cb56444f1a986d56e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Bark</topic><topic>Biological and medical sciences</topic><topic>Biological Transport - drug effects</topic><topic>Caco-2 Cells</topic><topic>Diabetes</topic><topic>Diabetes Mellitus - drug therapy</topic><topic>Enterocytes</topic><topic>Enterocytes - drug effects</topic><topic>Enterocytes - metabolism</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Feeding. Feeding behavior</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastroenterology and Hepatology</topic><topic>Glucose</topic><topic>Glucose - metabolism</topic><topic>Glucose Transporter Type 2 - antagonists & inhibitors</topic><topic>Glucose Transporter Type 2 - metabolism</topic><topic>Glucose transporter-2</topic><topic>Humans</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Insulin</topic><topic>Intestinal Absorption - drug effects</topic><topic>Kinases</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Membrane Transport Modulators - pharmacology</topic><topic>Mitogen activated protein kinase/extracellular signal-regulated kinase kinase</topic><topic>Mode of action</topic><topic>Na +-coupled glucose transport</topic><topic>p38 Mitogen-activated kinase</topic><topic>p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Phosphatidylinositol 3-Kinase - antagonists & inhibitors</topic><topic>Phosphatidylinositol 3-Kinase - metabolism</topic><topic>Phosphoinositol 3-kinase</topic><topic>Phytotherapy</topic><topic>Pine bark extract</topic><topic>Pinus - chemistry</topic><topic>Plant Bark - chemistry</topic><topic>Plant extracts</topic><topic>Plant Extracts - pharmacology</topic><topic>Proteins</topic><topic>Radioactivity</topic><topic>Sodium-Glucose Transporter 1 - antagonists & inhibitors</topic><topic>Sodium-Glucose Transporter 1 - metabolism</topic><topic>Sodium-Potassium-Exchanging ATPase - metabolism</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El-Zein, Ola, M.Sc</creatorcontrib><creatorcontrib>Kreydiyyeh, Sawsan Ibrahim, Ph.D</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Career & Technical Education Database</collection><collection>Nursing & Allied Health Database</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>British Nursing Index</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>British Nursing Index (BNI) (1985 to Present)</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>British Nursing Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Nutrition (Burbank, Los Angeles County, Calif.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El-Zein, Ola, M.Sc</au><au>Kreydiyyeh, Sawsan Ibrahim, Ph.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pine bark extract inhibits glucose transport in enterocytes via mitogen-activated kinase and phosphoinositol 3-kinase</atitle><jtitle>Nutrition (Burbank, Los Angeles County, Calif.)</jtitle><addtitle>Nutrition</addtitle><date>2011-06-01</date><risdate>2011</risdate><volume>27</volume><issue>6</issue><spage>707</spage><epage>712</epage><pages>707-712</pages><issn>0899-9007</issn><eissn>1873-1244</eissn><coden>NUTRER</coden><abstract>Abstract Objective Pine bark extract (PBE) has been reported to have hypoglycemic effects but its mode of action is still unclear. This work studied the effect of PBE on glucose uptake by Caco-2 cells in isolation of its effect on insulin, which may appear if ingested by the animal. Methods Caco-2 cells were incubated in the presence of PBE and [14 C] 3-O-methyl-D-glucose as a tracer and the change in radioactivity of the incubation medium was taken as a measurement of glucose uptake. To determine the mechanism of action of the extract and type of transporters involved, Na+ -coupled glucose transporter-1 (SGLT1) and glucose transporter-2 (GLUT2) and different signaling mediators known to be involved in glucose transport were inactivated by specific inhibitors. Changes in the protein expression of glucose transporters were studied by western blotting. Results The extract significantly decreased glucose transport but did not affect the activity or expression of Na+ /K+ adenosine triphosphatase. It was concluded that PBE affects the number of glucose transporters in the brush-border membrane. This conclusion was confirmed by western blot analysis. The results showed that the extract acts by activating p38 mitogen-activated kinase, which in turn activates SGLT1 transporters and two different pathways that target GLUT2: an inhibitory pathway involving phosphoinositol 3-kinase and a stimulatory pathway involving mitogen activated protein kinase/extracellular signal-regulated kinase kinase. The activity of the two pathways is orchestrated by SGLT1. Conclusion Pine bark extract inhibits glucose absorption by p38 mitogen-activated kinase and constitutes a potential complementary therapeutic or prophylactic agent for diabetes and its complications.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>20869203</pmid><doi>10.1016/j.nut.2010.07.001</doi><tpages>6</tpages></addata></record> |
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| subjects | Bark Biological and medical sciences Biological Transport - drug effects Caco-2 Cells Diabetes Diabetes Mellitus - drug therapy Enterocytes Enterocytes - drug effects Enterocytes - metabolism Enzyme Inhibitors - pharmacology Feeding. Feeding behavior Fundamental and applied biological sciences. Psychology Gastroenterology and Hepatology Glucose Glucose - metabolism Glucose Transporter Type 2 - antagonists & inhibitors Glucose Transporter Type 2 - metabolism Glucose transporter-2 Humans Hypoglycemic Agents - pharmacology Insulin Intestinal Absorption - drug effects Kinases MAP Kinase Signaling System - drug effects Membrane Transport Modulators - pharmacology Mitogen activated protein kinase/extracellular signal-regulated kinase kinase Mode of action Na +-coupled glucose transport p38 Mitogen-activated kinase p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors p38 Mitogen-Activated Protein Kinases - metabolism Phosphatidylinositol 3-Kinase - antagonists & inhibitors Phosphatidylinositol 3-Kinase - metabolism Phosphoinositol 3-kinase Phytotherapy Pine bark extract Pinus - chemistry Plant Bark - chemistry Plant extracts Plant Extracts - pharmacology Proteins Radioactivity Sodium-Glucose Transporter 1 - antagonists & inhibitors Sodium-Glucose Transporter 1 - metabolism Sodium-Potassium-Exchanging ATPase - metabolism Vertebrates: anatomy and physiology, studies on body, several organs or systems |
| title | Pine bark extract inhibits glucose transport in enterocytes via mitogen-activated kinase and phosphoinositol 3-kinase |
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