Sunday, October 6, 2024
10/6/2024
PROJECT SUMMARY The increase of obesity and diabetes in the US is associated with the highly palatable sugar content of the western diet. The sweet taste receptor (T1R2+T1R3) is historically known to be the primary detector of sugars and non-caloric sweeteners. However, recent investigations from my mentor demonstrated that mice with genetic deletion of T1R2+T1R3 (or its downstream signaling mechanisms, TRPM5) still prefer the taste of glucose and/maltose, suggesting the involvement of other orosensory receptors. The Schier lab recently identified a glucose sensor in taste bud cells, glucokinase (GCK), that is upregulated with sugar exposure and is required to rapidly detect and develop preference for glucose over fructose in sweet-sensitive mice. However, GCK does not directly engage with maltose. Therefore I hypothesized that the α-glucosidase, maltase glucoamylase (MGAM) generates free glucose ligands that activate nearby sweet receptors and/or GCK-linked sensors to drive licking for maltose. My preliminary findings show that MGAM is upregulated in response to sugar exposure and that virogenetic knockdown of either MGAM or GCK reduces the hedonic appeal of maltose in sweet-sensitive mice. In this proposal, I aim to enhance this research by determining if MGAM- and GCK-linked behaviors depend on TRPM5-mediated taste transduction (Aim 1). With additional training in fiber photometry, I further aim to understand how the taste signals generated by metabolically distinct sugars recruit the mesolimbic dopaminergic reward system to guide ingestive decisions (Aim 2). The overarching goal of these studies is to understand and link glucosensing mechanisms to the central gustatory reward axis.
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