{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:58:15Z","timestamp":1791568695963,"version":"4.3.4"},"reference-count":20,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1210\/en.2013-1529","type":"journal-article","created":{"date-parts":[[2013,8,20]],"date-time":"2013-08-20T00:26:13Z","timestamp":1376958373000},"page":"3978-3983","source":"Crossref","is-referenced-by-count":75,"title":["Oral l-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice"],"prefix":"10.1210","volume":"154","author":[{"given":"Christoffer","family":"Clemmensen","sequence":"first","affiliation":[{"name":"Division of Endocrinology Diabetes and Metabolism, Department of Internal Medicine (C.C., E.P.S., R.J.S., D.A.D., K.K.R.), University of Cincinnati College of Medicine, Cincinnati, Ohio 45237"},{"name":"Department of Drug Design and Pharmacology (C.C., S.S., H.B.-O.), Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanela","family":"Smajilovic","sequence":"first","affiliation":[{"name":"Department of Drug Design and Pharmacology (C.C., S.S., H.B.-O.), Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P.","family":"Smith","sequence":"first","affiliation":[{"name":"Division of Endocrinology Diabetes and Metabolism, Department of Internal Medicine (C.C., E.P.S., R.J.S., D.A.D., K.K.R.), University of Cincinnati College of Medicine, Cincinnati, Ohio 45237"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Woods","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience (S.C.W.), University of Cincinnati College of Medicine, Cincinnati, Ohio 45237"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Br\u00e4uner-Osborne","sequence":"first","affiliation":[{"name":"Department of Drug Design and Pharmacology (C.C., S.S., H.B.-O.), Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy J.","family":"Seeley","sequence":"first","affiliation":[{"name":"Division of Endocrinology Diabetes and Metabolism, Department of Internal Medicine (C.C., E.P.S., R.J.S., D.A.D., K.K.R.), University of Cincinnati College of Medicine, Cincinnati, Ohio 45237"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"D'Alessio","sequence":"first","affiliation":[{"name":"Division of Endocrinology Diabetes and Metabolism, Department of Internal Medicine (C.C., E.P.S., R.J.S., D.A.D., K.K.R.), University of Cincinnati College of Medicine, Cincinnati, Ohio 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