| First Author | Clemmensen C | Year | 2013 |
| Journal | Endocrinology | Volume | 154 |
| Issue | 11 | Pages | 3978-83 |
| PubMed ID | 23959939 | Mgi Jnum | J:203834 |
| Mgi Id | MGI:5528911 | Doi | 10.1210/en.2013-1529 |
| Citation | Clemmensen C, et al. (2013) Oral L-arginine stimulates GLP-1 secretion to improve glucose tolerance in male mice. Endocrinology 154(11):3978-83 |
| abstractText | 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. |
