lithium-chloride and Insulinoma

Central infusion of glucagon-like peptide-1-(7-36) amide (GLP-1) and intraperitoneal (i.p.) injection of lithium chloride (LiCl) produce similar patterns of c-Fos induction in the rat brain. These similarities led us to assess the hypothesis that neuronal activity caused by i.p. injection of LiCl involves activation of central GLP-1 pathways. We therefore determined if third-ventricular (i3vt) infusion of a GLP-1 receptor antagonist would block LiCl-induced c-Fos expression in the brainstem. Relative to rats pretreated with i3vt infusion of vehicle, pretreatment with the potent GLP-1 receptor antagonist, des His1 Glu9 exendin-4 (10.0 microgram), significantly attenuated LiCl-induced (76 mg/kg; i.p.) c-Fos expression in several brainstem regions, including the area postrema, the nucleus of the solitary tract, and the lateral parabrachial nucleus. While central infusion of des His1 Glu9 exendin-4 also blocked GLP-1-induced (10.0 microgram) anorexia and c-Fos expression, the antagonist produced no independent effects on food intake or c-Fos expression. These results suggest that LiCl-induced c-Fos expression in the rat brainstem is mediated, at least in part, by GLP-1 receptor signaling.

Topics: Animals; Brain Stem; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Guinea Pigs; Infusions, Parenteral; Injections, Intraperitoneal; Injections, Intraventricular; Insulin; Insulin Secretion; Insulinoma; Lithium Chloride; Male; Neurons; Peptide Fragments; Proto-Oncogene Proteins c-fos; Rats; Rats, Long-Evans; Receptors, Glucagon; Signal Transduction; Tumor Cells, Cultured