Glucagon-Like Peptide 1 and Taste Perception: From Molecular Mechanisms to Potential Clinical Implications

Abstract

Preclinical studies provided some important insights into the action of glucagon-like peptide 1 (GLP-1) in taste perception. This review examines the literature to uncover some molecular mechanisms and connections between GLP-1 and the gustatory coding. Local GLP-1 production in the taste bud cells, the expression of GLP-1 receptor on the adjacent nerves, a functional continuum in the perception of sweet chemicals from the gut to the tongue and an identification of GLP-1 induced signaling pathways in peripheral and central gustatory coding all strongly suggest that GLP-1 is involved in the taste perception, especially sweet. However, the impact of GLP-1 based therapies on gustatory coding in humans remains largely unaddressed. Based on the molecular background we encourage further exploration of the tongue as a new treatment target for GLP-1 receptor agonists in clinical studies. Given that pharmacological manipulation of gustatory coding may represent a new potential strategy against obesity and diabetes, the topic is of utmost clinical relevance.

Keywords: GLP-1; obesity; sweet; taste; tongue.

Figure 1

Taste sensation signaling and glucagon-like peptide 1 (GLP-1). Legend: A sugar molecule binds to heterodimeric G protein coupled receptor (GPCR) that consists of taste receptor type 1 member 2 (TAS1R2) and taste receptor type 1 member 3 (TAS1R3). Downstream signaling ultimately leads to release of ATP. Specifically, upon PLCβ2 activation IP3 as a second messenger is generated. IP3 releases intracellular Ca²⁺. Released Ca²⁺ gates transient receptor potential cation channel subfamily M member 5 (TRPM5), which results in cellular depolarization. The generated action potentials cause a release of ATP through voltage-gated calcium homeostasis modulator 1 (CALMH1) that engages purinergic receptors for ATP on the sensory nerve fibers. Sensory nerve fibers convey information to higher order neurons in the Nucleus Tractus Solitarus (NTS). Adenosine triphosphate (ATP) as a transmitter represents the major line of communication from TBC type II cells to the brain. In addition, when stimulated with sweet molecules, glucagon like peptide -1 (GLP-1) is also immediately released from TBCs by vesicular mechanisms. GLP-1 activates GLP-1 receptor (GLP-1 R) on the adjacent gustatory nerves. It seems that GLP-1 acts as ancillary neurotransmitter in cooperation with ATP for maximal activation of nerve fibers that transmit gustatory code for the perception of sweet.