Abstract
Glucagon-like peptide-1 (GLP-1) inhibits food intake and regulates glucose homeostasis. These actions are at least partly mediated by central GLP-1 receptor (GLP-1R). Little information is available, however, about the subcellular localization and the distribution of the GLP-1R protein in the rat brain. To determine the localization of GLP-1R protein in the rat brain, immunocytochemistry was performed at light and electron microscopic levels. The highest density of GLP-1R-immunoreactivity was observed in the circumventricular organs and regions in the vicinity of these areas like in the arcuate nucleus (ARC) and in the nucleus tractus solitarii (NTS). In addition, GLP-1R-immunreactive (IR) neuronal profiles were also observed in a number of telencephalic, diencephalic and brainstem areas and also in the cerebellum. Ultrastructural examination of GLP-1R-immunoreactivity in energy homeostasis related regions showed that GLP-1R immunoreactivity is associated with the membrane of perikarya and dendrites but GLP-1R can also be observed inside and on the surface of axon varicosities and axon terminals. In conclusion, in this study we provide a detailed map of the GLP-1R-IR structures in the CNS. Furthermore, we demonstrate that in addition to the perikaryonal and dendritic distribution, GLP-1R is also present in axonal profiles suggesting a presynaptic action of GLP-1. The very high concentration of GLP-1R-profiles in the circumventricular organs and in the ARC and NTS suggests that peripheral GLP-1 may influence brain functions via these brain areas.
Highlights
Glucagon-like peptide-1 (GLP-1) is an incretin hormone (Baggio and Drucker 2007)
The pattern of immunoreaction was very similar in WT mice (Fig. 1a, c, e, g) as it was observed in rats (Figs. 3, 4, 5, 6, 7 and 8) except in the circumventricular organs and most parts of the arcuate nucleus, which regions were almost completely filled with immunoreaction product in mice
We provide a detailed map of the GLP-1 receptor (GLP-1R)-immunoreactive profiles in the rat brain and describe the subcellular localization of this receptor
Summary
Glucagon-like peptide-1 (GLP-1) is an incretin hormone (Baggio and Drucker 2007). It is derived from the posttranslational processing of proglucagon (Baggio and Drucker 2007). This prohormone is synthesized by three cell populations, the neuroendocrine L cells of the intestinal
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