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

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.

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Publisher: Public Library of Science

Date Published: 17-December-2012

Author(s): Sandoval D., Barrera J., Stefater M., Sisley S., Woods S., D’Alessio D., Seeley R.

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

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