Arcuate Glucagon-Like Peptide 1 Receptors Regulate Glucose Homeostasis but Not Food Intake

OBJECTIVE—Glucagon-like peptide-1 (GLP-1) promotes glu-cose homeostasis through regulation of islet hormone secretion, as well as hepatic and gastric function. Because GLP-1 is also synthesized in the brain, where it regulates food intake, we hypothesized that the central GLP-1 system regulates glucose tolerance as well. RESEARCH DESIGN AND METHODS—We used glucose tolerance tests and hyperinsulinemic-euglycemic clamps to as-sess the role of the central GLP-1 system on glucose tolerance, insulin secretion, and hepatic and peripheral insulin sensitivity. Finally, in situ hybridization was used to examine colocalization of GLP-1 receptors with neuropeptide tyrosine and pro-opiomela-nocortin neurons. RESULTS—We found that central, but not peripheral, adminis-tration of low doses of a GLP-1 receptor antagonist cause