Central Functions of Glucagon-like Peptide-1: Roles in Energy Regulation andNeuroprotection

The identification of the glucagon-like peptide-1 receptor in the central nervous system has led to an array of studies exploring the functions of central GLP-1 signalling. Originally identified as a gastrointestinal incretin hormone responsible for the potentiation of insulin secretion following ingestion of nutrients, the role of GLP-1 has been expanded to include specific neural activities. Two distinct actions of GLP-1 receptor activation in the brain have been identified, namely the regulation of appetite via promotion of satiety, as well as anti-inflammatory and anti-apoptotic activity to promote neuronal cell survival. Both of these features are now being exploited clinically, with GLP-1 receptor agonists, initially designed and marketed for the treatment of hyperglycaemia in type 2 diabetes, now being directed towards use in obesity and as potential neuroprotective agents. This review gives a summary of the functional role of GLP-1 in the central nervous system, in terms of promoting satiety, modulating food intake and aiding in the regulation of peripheral glycaemia. In addition, the molecular mechanisms underpinning the beneficial effects of central GLP-1 receptor agonist therapy in protecting against neuronal cell inflammation and death, including neurodegenerative processes, are described.