%0 Journal Article
%T Liraglutide Suppresses the Plasma Levels of Active and Des-Acyl Ghrelin Independently of Active Glucagon-Like Peptide-1 Levels in Mice
%A Katsunori Nonogaki
%A Marina Suzuki
%J ISRN Endocrinology
%D 2013
%R 10.1155/2013/184753
%X Glucagon-like peptide-1 (GLP-1), an insulinotropic gastrointestinal peptide that is primarily produced by intestinal endocrine L-cells, stimulates satiety. Ghrelin, a hormone that is produced predominantly by the stomach stimulates hunger. There are two forms of ghrelin: active ghrelin and inactive des-acyl ghrelin. After depriving mice of food for 24£¿h, we demonstrated that the systemic administration of liraglutide (100£¿¦Ìg/kg), a human GLP-1 analog that binds to the GLP-1 receptor, increased (1.4-fold) the plasma levels of active GLP-1 and suppressed the plasma levels of active and des-acyl ghrelin after 1£¿h. Despite the elevated plasma levels of active GLP-1 (11-fold), liraglutide had no effect on the plasma levels of active or des-acyl ghrelin after 12£¿h. These findings demonstrated that liraglutide suppresses the plasma levels of active and des-acyl ghrelin independently of active GLP-1 levels in fasted mice, suggesting a novel in vivo biological effect of liraglutide beyond regulating plasma GLP-1. 1. Introduction Hunger is stimulated by ghrelin, a hormone that is primarily produced by the P/D1 cells that line the fundus of the stomach [1]. Plasma ghrelin levels increase during fasting and decrease after ingesting glucose or lipids but not protein [1]. The efferent vagus nerve contributes to the fasting-induced increase in ghrelin secretion [1, 2]. The ghrelin that is secreted in the stomach stimulates the afferent vagus nerve and promotes food intake [1]. Ghrelin exists in both inactive (des-acyl ghrelin) and active forms. Fasting increases both forms of ghrelin compared with the fed state. Hyperphagia and obesity decrease the plasma levels of des-acyl ghrelin but not of active ghrelin [1]. Satiety is stimulated by glucagon-like peptide-1 (GLP-1), an incretin hormone that is released from intestinal L-cells in response to nutrient ingestion [3¨C5]. The GLP-1 receptors (GLP-1Rs) are expressed in the central nervous system (CNS) and the afferent vagal nerve terminals and contribute to the anorexic effect of GLP-1 [3¨C6]. GLP-1 potentiates glucose-dependent insulin secretion by activating the GLP-1Rs that are expressed on pancreatic islet ¦Â cells [3¨C5]. GLP-1 secretion increases after ingesting glucose and lipids but not protein [6]. In the isolated rat stomach, GLP-1 has been reported to suppress ghrelin release [7]. In addition, GLP-1 suppresses plasma ghrelin levels in humans via insulin secretion in the late postprandial period [8]. Once GLP-1 is released from the L cells into the bloodstream, it is rapidly degraded from its active form (7¨C36) to
%U http://www.hindawi.com/journals/isrn.endocrinology/2013/184753/