The sweet taste receptor protein T1r2+T1r3, encoded by the Tas1r2 and Tas1r3 genes, mediates taste responses to non-caloric sweeteners. However, Tas1r3 knockout mice generated in our group retain taste nerve responses to glucose and maltose. Glucose transporters (GLUTs) and metabolic sensors (KATP) expressed selectively in Tas1r3-positive taste cells may underlie taste responses of Tas1r3 knockout mice to sugars. Tas1r3-positive taste cells also express two intestinal type enzymes, sucrase-isomaltase and maltase-glucoamylase, that hydrolyze sucrose and maltose. The general goals of this grant are to elucidate the mechanisms underlying taste detection of sugars and to identify transcription factors that control the generation of sweet-responsive taste cells. The experiments proposed here use gene knockout mice and enzyme inhibitors to assess the involvement of KATP, sucrase-isomaltase and maltase-glucoamylase in taste responses to sugars. In the first two aims of the proposal we combine transgenic, physiological and behavioral methods to determine: 1. If sugar transporters and KATP metabolic sensors contribute to taste transduction of sugars, and 2. If intestinal disaccharidase enzymes expressed in Tas1r3-positive taste cells contribute to taste transduction of sugars. In the third aim we build on results from bioinformatic analysis of genes expressed in taste cells to: (a) Identify transcription factors selectively expressed in Tas1r3+ taste cells, and (b) Determine if loss of transcription factors selectively expressed in Tas1r3-positive taste cells affects generation and function of these cells. Ultimately, these studies may provide insights into why sugars are preferred over non-caloric sweeteners, lead to the generation of superior non-caloric sweeteners, and provide a means to regulate sweet-responsive taste cells so as to decrease the drive for consuming sugar. This multidisciplinary approach has promise for providing significant new insights into the function and regulation of sweet taste receptor cells. This proposal has medical relevance to gustatory function, appetite, satiety, diabetes and obesity.

Public Health Relevance

Knockout mice lacking T1r3, a required component of the sweet receptor protein, lose nerve responses to non-caloric sweeteners, but still respond well to glucose and other sugars. The experiments proposed will determine if ATP-gated K+ channels and intestinal type disaccharidase enzymes expressed in sweet taste receptor cells contribute to taste detection of sugars. Other experiments will seek to identify transcription factors that regulate the generation and function of sweet taste receptor cells. The work proposed has medical relevance to gustatory function, appetite, satiety, diabetes and obesity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC014105-02
Application #
9015425
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2015-03-01
Project End
2020-02-29
Budget Start
2016-03-01
Budget End
2017-02-28
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Monell Chemical Senses Center
Department
Type
DUNS #
088812565
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Sukumaran, Sunil K; Lewandowski, Brian C; Qin, Yumei et al. (2017) Whole transcriptome profiling of taste bud cells. Sci Rep 7:7595
Lee, Robert J; Hariri, Benjamin M; McMahon, Derek B et al. (2017) Bacterial d-amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells. Sci Signal 10:
Ren, Wenwen; Aihara, Eitaro; Lei, Weiwei et al. (2017) Transcriptome analyses of taste organoids reveal multiple pathways involved in taste cell generation. Sci Rep 7:4004
Lewandowski, Brian C; Sukumaran, Sunil K; Margolskee, Robert F et al. (2016) Amiloride-Insensitive Salt Taste Is Mediated by Two Populations of Type III Taste Cells with Distinct Transduction Mechanisms. J Neurosci 36:1942-53
Sukumaran, Sunil K; Yee, Karen K; Iwata, Shusuke et al. (2016) Taste cell-expressed ?-glucosidase enzymes contribute to gustatory responses to disaccharides. Proc Natl Acad Sci U S A 113:6035-40
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Glendinning, John I; Stano, Sarah; Holter, Marlena et al. (2015) Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice. Am J Physiol Regul Integr Comp Physiol 309:R552-60
Takai, Shingo; Yasumatsu, Keiko; Inoue, Mayuko et al. (2015) Glucagon-like peptide-1 is specifically involved in sweet taste transmission. FASEB J 29:2268-80

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