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

Publication ,  Journal Article
Clemmensen, C; Smajilovic, S; Smith, EP; Woods, SC; Bräuner-Osborne, H; Seeley, RJ; D'Alessio, DA; Ryan, KK
Published in: Endocrinology
November 2013

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.

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Published In

Endocrinology

DOI

EISSN

1945-7170

Publication Date

November 2013

Volume

154

Issue

11

Start / End Page

3978 / 3983

Location

United States

Related Subject Headings

  • Receptors, Glucagon
  • Obesity
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Insulin
  • Glucose Tolerance Test
  • Glucose Intolerance
  • Glucagon-Like Peptide-1 Receptor
 

Citation

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Clemmensen, C., Smajilovic, S., Smith, E. P., Woods, S. C., Bräuner-Osborne, H., Seeley, R. J., … Ryan, K. K. (2013). Oral L-arginine stimulates GLP-1 secretion to improve glucose tolerance in male mice. Endocrinology, 154(11), 3978–3983. https://doi.org/10.1210/en.2013-1529
Clemmensen, Christoffer, Sanela Smajilovic, Eric P. Smith, Stephen C. Woods, Hans Bräuner-Osborne, Randy J. Seeley, David A. D’Alessio, and Karen K. Ryan. “Oral L-arginine stimulates GLP-1 secretion to improve glucose tolerance in male mice.Endocrinology 154, no. 11 (November 2013): 3978–83. https://doi.org/10.1210/en.2013-1529.
Clemmensen C, Smajilovic S, Smith EP, Woods SC, Bräuner-Osborne H, Seeley RJ, et al. Oral L-arginine stimulates GLP-1 secretion to improve glucose tolerance in male mice. Endocrinology. 2013 Nov;154(11):3978–83.
Clemmensen, Christoffer, et al. “Oral L-arginine stimulates GLP-1 secretion to improve glucose tolerance in male mice.Endocrinology, vol. 154, no. 11, Nov. 2013, pp. 3978–83. Pubmed, doi:10.1210/en.2013-1529.
Clemmensen C, Smajilovic S, Smith EP, Woods SC, Bräuner-Osborne H, Seeley RJ, D’Alessio DA, Ryan KK. Oral L-arginine stimulates GLP-1 secretion to improve glucose tolerance in male mice. Endocrinology. 2013 Nov;154(11):3978–3983.
Journal cover image

Published In

Endocrinology

DOI

EISSN

1945-7170

Publication Date

November 2013

Volume

154

Issue

11

Start / End Page

3978 / 3983

Location

United States

Related Subject Headings

  • Receptors, Glucagon
  • Obesity
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Insulin
  • Glucose Tolerance Test
  • Glucose Intolerance
  • Glucagon-Like Peptide-1 Receptor