Oral L-arginine stimulates GLP-1 secretion to improve glucose tolerance in male mice.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Clemmensen, C; Smajilovic, S; Smith, EP; Woods, SC; Bräuner-Osborne, H; Seeley, RJ; D'Alessio, DA; Ryan, KK

Published Date

  • November 2013

Published In

Volume / Issue

  • 154 / 11

Start / End Page

  • 3978 - 3983

PubMed ID

  • 23959939

Pubmed Central ID

  • PMC3800753

Electronic International Standard Serial Number (EISSN)

  • 1945-7170

Digital Object Identifier (DOI)

  • 10.1210/en.2013-1529


  • eng

Conference Location

  • United States