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The anorectic effect of GLP-1 in rats is nutrient dependent.

Publication ,  Journal Article
Sandoval, D; Barrera, JG; Stefater, MA; Sisley, S; Woods, SC; D'Alessio, DD; Seeley, RJ
Published in: PLoS One
2012

GLP-1-induced insulin secretion from the β-cell is dependent upon glucose availability. The purpose of the current study was to determine whether CNS GLP-1 signaling is also glucose-dependent. We found that fasting blunted the ability of 3(rd) cerebroventricularly (i3vt)-administered GLP-1 to reduce food intake. However, fasted animals maintained the anorexic response to melanotan II, a melanocortin receptor agonist, indicating a specific effect of fasting on GLP-1 action. We also found that i3vt administration of leptin, which is also decreased with fasting, was not able to potentiate GLP-1 action in fasted animals. However, we did find that CNS glucose sensing is important in GLP-1 action. Specifically, we found that i3vt injection of 2DG, a drug that blocks cellular glucose utilization, and AICAR which activates AMPK, both blocked GLP-1-induced reductions in food intake. To examine the role of glucokinase, an important CNS glucose sensor, we studied glucokinase-heterozygous knockout mice, but found that they responded normally to peripherally administered GLP-1 and exendin-4. Interestingly, oral, but not i3vt or IP glucose potentiated GLP-1's anorectic action. Thus, CNS and peripheral fuel sensing are both important in GLP-1-induced reductions in food intake.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

12

Start / End Page

e51870

Location

United States

Related Subject Headings

  • Ribonucleotides
  • Rats, Long-Evans
  • Rats
  • Protein Kinases
  • Mice, Knockout
  • Mice
  • Male
  • Incretins
  • Heterozygote
  • Glucose
 

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Sandoval, D., Barrera, J. G., Stefater, M. A., Sisley, S., Woods, S. C., D’Alessio, D. D., & Seeley, R. J. (2012). The anorectic effect of GLP-1 in rats is nutrient dependent. PLoS One, 7(12), e51870. https://doi.org/10.1371/journal.pone.0051870
Sandoval, Darleen, Jason G. Barrera, Margaret A. Stefater, Stephanie Sisley, Stephen C. Woods, David D. D’Alessio, and Randy J. Seeley. “The anorectic effect of GLP-1 in rats is nutrient dependent.PLoS One 7, no. 12 (2012): e51870. https://doi.org/10.1371/journal.pone.0051870.
Sandoval D, Barrera JG, Stefater MA, Sisley S, Woods SC, D’Alessio DD, et al. The anorectic effect of GLP-1 in rats is nutrient dependent. PLoS One. 2012;7(12):e51870.
Sandoval, Darleen, et al. “The anorectic effect of GLP-1 in rats is nutrient dependent.PLoS One, vol. 7, no. 12, 2012, p. e51870. Pubmed, doi:10.1371/journal.pone.0051870.
Sandoval D, Barrera JG, Stefater MA, Sisley S, Woods SC, D’Alessio DD, Seeley RJ. The anorectic effect of GLP-1 in rats is nutrient dependent. PLoS One. 2012;7(12):e51870.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

12

Start / End Page

e51870

Location

United States

Related Subject Headings

  • Ribonucleotides
  • Rats, Long-Evans
  • Rats
  • Protein Kinases
  • Mice, Knockout
  • Mice
  • Male
  • Incretins
  • Heterozygote
  • Glucose