Endocrine Abstracts (2012) 28 P224

A comparison of the neuronal populations within the nucleus tractus solitarius activated by peripheral administration of glucagon, GLP-1 and oxyntomodulin

Jennifer Parker, John Tadross, Benjamin Field, James Minnion & Stephen Bloom

Diabetes, Endocrinology and Metabolism, Imperial College, London, United Kingdom.

The preproglucagon derived peptides glucagon, glucagon-like peptide-1 (GLP-1) and oxyntomodulin are all known to inhibit appetite and have been previously shown to activate the nucleus tractus solitarius (NTS) in the brainstem. The NTS is involved in the processing of signals transmitted from the periphery to the brain via the vagus nerve. The anorectic effects of peripherally administered glucagon and GLP-1 have been shown to be diminished or ablated by subdiaphragmatic vagotomy and by brainstem-hypothalamic transection. This suggests processing of vagal signals in the NTS is likely to be of significant importance in mediating the anorectic effects of these peptides. Whilst glucagon, GLP-1 and oxyntomodulin are all anorectic, it is not known whether the mechanism is the same. GLP-1 and oxyntomodulin are thought to act via GLP-1 receptors to inhibit food intake, whereas the affinity of glucagon for the GLP-1 receptor is very low and thus it more likely acts via the glucagon receptor. Oxyntomodulin is a dual agonist at the GLP-1 and glucagon receptors. It is therefore possible that oxyntomodulin may induce anorexia by two independent pathways. The current study aimed to characterise the populations of neurons within the NTS activated by glucagon, GLP-1 and oxyntomodulin, using dual immunohistochemistry for c-fos and for markers which describe four major populations in this area: catecholamine, preproglucagon, CART and POMC expressing neurons. In addition, a comparison was made between the pattern of c-fos expression induced by equivalently anorectic doses of GLP-1, glucagon and oxyntomodulin across a range of appetite regulating centres in the brain. The identification of neuronal populations activated by these hormones in the NTS and the direct comparison of c-fos expression induced of appetite regulating centres sheds new light on the degree to which the anorectic mechanisms of GLP-1, glucagon and oxyntomodulin converge in the CNS.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.

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