title: Oral L-arginine stimulates GLP-1 secretion to improve glucose tolerance in male mice.
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.
authors: 2170 East Galbraith Road, A125, Cincinnati, Ohio 45237. karen.ryan@uc.edu.
authors: Christoffer
authors: C
authors: Clemmensen
authors: Sanela
authors: S
authors: Smajilovic
authors: Eric P
authors: EP
authors: Smith
authors: Stephen C
authors: SC
authors: Woods
authors: Hans
authors: H
authors: Bräuner-Osborne
authors: Randy J
authors: RJ
authors: Seeley
authors: David A
authors: DA
authors: D'Alessio
authors: Karen K
authors: KK
authors: Ryan
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D018149:Glucose Intolerance / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D001120:Arginine
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