Oral l-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice
Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet-induced obes...
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description | Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet-induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1 and insulin and substantially improved glucose clearance. To directly assess the contribution of GLP-1 receptor (GLP-1R)-signaling to these improvements, l-arginine was given to Glp1r knockout mice and their wild-type littermates. In this experiment oral l-arginine significantly augmented insulin secretion and improved glucose clearance in WT mice, but not in Glp1r knockout littermates. Taken together these findings identify l-arginine as a GLP-1 secretagogue in vivo and demonstrate that improvement of glucose tolerance by oral l-arginine depends on GLP-1R-signaling. These findings raise the intriguing possibility that l-arginine-based nutritional and/or pharmaceutical therapies may benefit glucose tolerance by improving the postprandial GLP-1 response in obese individuals. |
doi_str_mv | 10.1210/en.2013-1529 |
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In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet-induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1 and insulin and substantially improved glucose clearance. To directly assess the contribution of GLP-1 receptor (GLP-1R)-signaling to these improvements, l-arginine was given to Glp1r knockout mice and their wild-type littermates. In this experiment oral l-arginine significantly augmented insulin secretion and improved glucose clearance in WT mice, but not in Glp1r knockout littermates. Taken together these findings identify l-arginine as a GLP-1 secretagogue in vivo and demonstrate that improvement of glucose tolerance by oral l-arginine depends on GLP-1R-signaling. These findings raise the intriguing possibility that l-arginine-based nutritional and/or pharmaceutical therapies may benefit glucose tolerance by improving the postprandial GLP-1 response in obese individuals.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2013-1529</identifier><identifier>PMID: 23959939</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Chevy Chase, MD: Endocrine Society</publisher><subject>Amino acids ; Animals ; Arginine ; Arginine - pharmacology ; Biological and medical sciences ; Brief Research Reports ; Clearances ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diet ; Dietary Fats - pharmacology ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation - drug effects ; Glucagon ; Glucagon-like peptide 1 ; Glucagon-Like Peptide 1 - genetics ; Glucagon-Like Peptide 1 - metabolism ; Glucagon-Like Peptide-1 Receptor ; Glucose ; Glucose Intolerance - drug therapy ; Glucose tolerance ; Glucose Tolerance Test ; Homeostasis ; In vivo methods and tests ; Insulin ; Insulin - blood ; Insulin secretion ; Intestine ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity ; Obesity - chemically induced ; Obesity - metabolism ; Receptors, Glucagon - genetics ; Receptors, Glucagon - metabolism ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2013-11, Vol.154 (11), p.3978-3983</ispartof><rights>Copyright © 2013 by The Endocrine Society</rights><rights>Copyright © 2013 by The Endocrine Society 2013</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c584t-b8a5e49f27f778bb5a28f0df3ce7313ffe3fefcab0670d2ef9110bae6cb229dd3</citedby><cites>FETCH-LOGICAL-c584t-b8a5e49f27f778bb5a28f0df3ce7313ffe3fefcab0670d2ef9110bae6cb229dd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27914679$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23959939$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Clemmensen, Christoffer</creatorcontrib><creatorcontrib>Smajilovic, Sanela</creatorcontrib><creatorcontrib>Smith, Eric P</creatorcontrib><creatorcontrib>Woods, Stephen C</creatorcontrib><creatorcontrib>Bräuner-Osborne, Hans</creatorcontrib><creatorcontrib>Seeley, Randy J</creatorcontrib><creatorcontrib>D'Alessio, David A</creatorcontrib><creatorcontrib>Ryan, Karen K</creatorcontrib><title>Oral l-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet-induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1 and insulin and substantially improved glucose clearance. To directly assess the contribution of GLP-1 receptor (GLP-1R)-signaling to these improvements, l-arginine was given to Glp1r knockout mice and their wild-type littermates. In this experiment oral l-arginine significantly augmented insulin secretion and improved glucose clearance in WT mice, but not in Glp1r knockout littermates. Taken together these findings identify l-arginine as a GLP-1 secretagogue in vivo and demonstrate that improvement of glucose tolerance by oral l-arginine depends on GLP-1R-signaling. These findings raise the intriguing possibility that l-arginine-based nutritional and/or pharmaceutical therapies may benefit glucose tolerance by improving the postprandial GLP-1 response in obese individuals.</description><subject>Amino acids</subject><subject>Animals</subject><subject>Arginine</subject><subject>Arginine - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Brief Research Reports</subject><subject>Clearances</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diet</subject><subject>Dietary Fats - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Glucagon</subject><subject>Glucagon-like peptide 1</subject><subject>Glucagon-Like Peptide 1 - genetics</subject><subject>Glucagon-Like Peptide 1 - metabolism</subject><subject>Glucagon-Like Peptide-1 Receptor</subject><subject>Glucose</subject><subject>Glucose Intolerance - drug therapy</subject><subject>Glucose tolerance</subject><subject>Glucose Tolerance Test</subject><subject>Homeostasis</subject><subject>In vivo methods and tests</subject><subject>Insulin</subject><subject>Insulin - blood</subject><subject>Insulin secretion</subject><subject>Intestine</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Obesity</subject><subject>Obesity - chemically induced</subject><subject>Obesity - metabolism</subject><subject>Receptors, Glucagon - genetics</subject><subject>Receptors, Glucagon - metabolism</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kd1LHDEUxYNYdLV987kERHzp2HzMbCYvgki7FVYU3D6HTOZGI7PJNJkR_O-bYbd-QH0KSX6cc-49CB1RckYZJd_BnzFCeUErJnfQjMqyKgQVZBfNyPQuGBP76CClx3wty5LvoX3GZSUllzO0uom6w11xEe-ddx7w3eDWY6cHSHixvC0ovgMTYXDB4yHgq3UfwxPgRTeakACvQgdRewPYeXytO8DXzsBn9MnqLsGX7XmIfv_8sbr8VSxvFleXF8vCVHU5FE2tKyilZcIKUTdNpVltSWu5AcEptxa4BWt0Q-aCtAyspJQ0GuamYUy2LT9E5xvdfmzW0BrwQ55G9dGtdXxWQTv1_se7B3UfnhSvCREVzwLHW4EY_oyQBvUYxuhzZpUDkDmrKa0y9W1DmRhSimBfHChRUwcKvJo6UFMHGf_6NtUL_G_pGTjZAjoZ3dlpgS69ckLSci4m7nTDhbH_yLLYWvINCb4NJuYe-wgpvU7z36B_AYyErMg</recordid><startdate>20131101</startdate><enddate>20131101</enddate><creator>Clemmensen, Christoffer</creator><creator>Smajilovic, Sanela</creator><creator>Smith, Eric P</creator><creator>Woods, Stephen C</creator><creator>Bräuner-Osborne, Hans</creator><creator>Seeley, Randy J</creator><creator>D'Alessio, David A</creator><creator>Ryan, Karen K</creator><general>Endocrine Society</general><general>Oxford University Press</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>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20131101</creationdate><title>Oral l-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice</title><author>Clemmensen, Christoffer ; Smajilovic, Sanela ; Smith, Eric P ; Woods, Stephen C ; Bräuner-Osborne, Hans ; Seeley, Randy J ; D'Alessio, David A ; Ryan, Karen K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c584t-b8a5e49f27f778bb5a28f0df3ce7313ffe3fefcab0670d2ef9110bae6cb229dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amino acids</topic><topic>Animals</topic><topic>Arginine</topic><topic>Arginine - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Brief Research Reports</topic><topic>Clearances</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diet</topic><topic>Dietary Fats - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Glucagon</topic><topic>Glucagon-like peptide 1</topic><topic>Glucagon-Like Peptide 1 - genetics</topic><topic>Glucagon-Like Peptide 1 - metabolism</topic><topic>Glucagon-Like Peptide-1 Receptor</topic><topic>Glucose</topic><topic>Glucose Intolerance - drug therapy</topic><topic>Glucose tolerance</topic><topic>Glucose Tolerance Test</topic><topic>Homeostasis</topic><topic>In vivo methods and tests</topic><topic>Insulin</topic><topic>Insulin - blood</topic><topic>Insulin secretion</topic><topic>Intestine</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Obesity</topic><topic>Obesity - chemically induced</topic><topic>Obesity - metabolism</topic><topic>Receptors, Glucagon - genetics</topic><topic>Receptors, Glucagon - metabolism</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Clemmensen, Christoffer</creatorcontrib><creatorcontrib>Smajilovic, Sanela</creatorcontrib><creatorcontrib>Smith, Eric P</creatorcontrib><creatorcontrib>Woods, Stephen C</creatorcontrib><creatorcontrib>Bräuner-Osborne, Hans</creatorcontrib><creatorcontrib>Seeley, Randy J</creatorcontrib><creatorcontrib>D'Alessio, David A</creatorcontrib><creatorcontrib>Ryan, Karen K</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>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Clemmensen, Christoffer</au><au>Smajilovic, Sanela</au><au>Smith, Eric P</au><au>Woods, Stephen C</au><au>Bräuner-Osborne, Hans</au><au>Seeley, Randy J</au><au>D'Alessio, David A</au><au>Ryan, Karen K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oral l-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2013-11-01</date><risdate>2013</risdate><volume>154</volume><issue>11</issue><spage>3978</spage><epage>3983</epage><pages>3978-3983</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet-induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1 and insulin and substantially improved glucose clearance. To directly assess the contribution of GLP-1 receptor (GLP-1R)-signaling to these improvements, l-arginine was given to Glp1r knockout mice and their wild-type littermates. In this experiment oral l-arginine significantly augmented insulin secretion and improved glucose clearance in WT mice, but not in Glp1r knockout littermates. Taken together these findings identify l-arginine as a GLP-1 secretagogue in vivo and demonstrate that improvement of glucose tolerance by oral l-arginine depends on GLP-1R-signaling. These findings raise the intriguing possibility that l-arginine-based nutritional and/or pharmaceutical therapies may benefit glucose tolerance by improving the postprandial GLP-1 response in obese individuals.</abstract><cop>Chevy Chase, MD</cop><pub>Endocrine Society</pub><pmid>23959939</pmid><doi>10.1210/en.2013-1529</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino acids Animals Arginine Arginine - pharmacology Biological and medical sciences Brief Research Reports Clearances Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diet Dietary Fats - pharmacology Fundamental and applied biological sciences. Psychology Gene Expression Regulation - drug effects Glucagon Glucagon-like peptide 1 Glucagon-Like Peptide 1 - genetics Glucagon-Like Peptide 1 - metabolism Glucagon-Like Peptide-1 Receptor Glucose Glucose Intolerance - drug therapy Glucose tolerance Glucose Tolerance Test Homeostasis In vivo methods and tests Insulin Insulin - blood Insulin secretion Intestine Male Mice Mice, Inbred C57BL Mice, Knockout Obesity Obesity - chemically induced Obesity - metabolism Receptors, Glucagon - genetics Receptors, Glucagon - metabolism Vertebrates: endocrinology |
title | Oral l-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice |
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