The Anorectic Effect of GLP-1 in Rats Is Nutrient Dependent

22Citations
Citations of this article
34Readers
Mendeley users who have this article in their library.

Abstract

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 3rd 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. © 2012 Sandoval et al.

Cite

CITATION STYLE

APA

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). https://doi.org/10.1371/journal.pone.0051870

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free