ABSTRACT
GLP-1 is coproduced and cosecreted with GLP-2 and oxyntomodulin from the preproglucagon precursor molecule in two sites in the body: (1) enteroendocrine L cells interspersed
in the epithelium of the gut (from the duodenum to the colon) and (2) a small population of neurons in the nucleus of the solitary tract (NTS) (for reviews, see the studies by Holst3 and Vrang et al.4). Gut luminal nutrients stimulate L cells to secrete GLP-1, which in turn potentiates glucose-induced insulin secretion (the incretin effect).1-3
In the brain, GLP-1 production is restricted to a small population of neurons in the caudal part of the NTS.5,6 The NTS receives input from the vagus nerve (vagal afferents), and the part of the NTS harboring the GLP-1 neurons receives intestinal vagal afferents from the gut.7,8 Consistent with this, it has been shown that activation of the vagal afferents either by gastric distension or by various chemicals activates the brain stem GLP-1 system.9,10 From their location in the NTS, the brain stem GLP-1 neurons primarily project to hypothalamic sites involved in food and water intake regulation,5,6,11,12 but this small population of neurons also targets numerous other areas in the forebrain and the brain stem (for a review, see the study by Vrang et al.4). A large number of studies have consistently shown that the central administration of GLP-1 leads to a reduction in food intake,13-24 and it is generally accepted that the activation of brain stem GLP-1 neurons and the subsequent release of GLP-1 in hypothalamic and brain stem target sites expressing the GLP-1 receptor lead to a suppression in food intake.
