Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Noriatsu Shigemura Last modified date:2021.06.28

Professor / Oral Biological Sciences / Department of Dental Science / Faculty of Dental Science

1. Yamada Y, Takai S, Watanabe Y, Osaki A, Kawabata Y, Oike A, Hirayama A, Iwata S, Sanematsu K, Tabata S, Shigemura N., Gene expression profiling of α-gustducin-expressing taste cells in mouse fungiform and circumvallate papillae , Biochem Biophys Res Commun., 10.1016/j.bbrc.2021.04.022, 557, 206-212, 2021.04.
2. Osaki A, Sanematsu K, Yamazoe J, Hirose F, Watanabe Y, Kawabata Y, Oike A, Hirayama A, Yamada Y, Iwata S, Takai S, Wada N, Shigemura N, Drinking Ice-cold Water Reduces the Severity of Anticancer Drug-induced Taste Dysfunction in Mice, Int J Mol Sci., 10.3390/ijms21238958, 21, (23), 8958, 2020.11, Taste disorders are common adverse effects of cancer chemotherapy that can reduce quality of life and impair nutritional status. However, the molecular mechanisms underlying chemotherapy-induced taste disorders remain largely unknown. Furthermore, there are no effective preventive measures for chemotherapy-induced taste disorders. We investigated the effects of a combination of three anticancer drugs (TPF: docetaxel, cisplatin and 5-fluorouracil) on the structure and function of mouse taste tissues and examined whether the drinking of ice-cold water after TPF administration would attenuate these effects. TPF administration significantly increased the number of cells expressing apoptotic and proliferative markers. Furthermore, TPF administration significantly reduced the number of cells expressing taste cell markers and the magnitudes of the responses of taste nerves to tastants. The above results suggest that anticancer drug-induced taste dysfunction may be due to a reduction in the number of taste cells expressing taste-related molecules. The suppressive effects of TPF on taste cell marker expression and taste perception were reduced by the drinking of ice-cold water. We speculate that oral cryotherapy with an ice cube might be useful for prophylaxis against anticancer drug-induced taste disorders in humans..
3. Michimasa Masamoto, Yoshihiro Mitoh, Motoi Kobashi, Noriatsu Shigemura, Ryusuke Yoshida, Effects of Bitter Receptor Antagonists on Behavioral Lick Responses of Mice, Neurosci Lett., 10.1016/j.neulet.2020.135041, 730, 135041, 2020.06.
4. Takai S, Shigemura N., Insulin Function in Peripheral Taste Organ Homeostasis, Curr Oral Health Rep., 10.1007/s40496-020-00266-2, 730, 2020.05.
5. Fumie Hirose, Shingo Takai, Ichiro Takahashi, Noriatsu Shigemura, Expression of protocadherin-20 in mouse taste buds, Scientific reports, 10.1038/s41598-020-58991-8, 10, 1, 2020.12, Taste information is detected by taste cells and then transmitted to the brain through the taste nerve fibers. According to our previous data, there may be specific coding of taste quality between taste cells and nerve fibers. However, the molecular mechanisms underlying this coding specificity remain unclear. The purpose of this study was to identify candidate molecules that may regulate the specific coding. GeneChip analysis of mRNA isolated from the mice taste papillae and taste ganglia revealed that 14 members of the cadherin superfamily, which are important regulators of synapse formation and plasticity, were expressed in both tissues. Among them, protocadherin-20 (Pcdh20) was highly expressed in a subset of taste bud cells, and co-expressed with taste receptor type 1 member 3 (T1R3, a marker of sweet- or umami-sensitive taste cells) but not gustducin or carbonic anhydrase-4 (markers of bitter/sweet- and sour-sensitive taste cells, respectively) in circumvallate papillae. Furthermore, Pcdh20 expression in taste cells occurred later than T1R3 expression during the morphogenesis of taste papillae. Thus, Pcdh20 may be involved in taste quality-specific connections between differentiated taste cells and their partner neurons, thereby acting as a molecular tag for the coding of sweet and/or umami taste..
6. Shigemura N, Takai S, Hirose F, Yoshida R, Sanematsu K, Ninomiya Y., Expression of Renin-Angiotensin System Components in the Taste Organ of Mice, Nutrients., 10.3390/nu11092251, 11, 9, 11(9). pii: E2251, 2019.09.
7. Jihye Park, Balaji Selvam, Keisuke Sanematsu, Noriatsu Shigemura, Diwakar Shukla, Erik Procko, Structural architecture of a dimeric class C GPCR based on co-trafficking of sweet taste receptor subunits, Journal of Biological Chemistry, 10.1074/jbc.RA118.006173, 294, 13, 4759-4774, 2019.03, Class C G protein– coupled receptors (GPCRs) are obligatory dimers that are particularly important for neuronal responses to endogenous and environmental stimuli. Ligand recognition through large extracellular domains leads to the reorganization of transmembrane regions to activate G protein signaling. Although structures of individual domains are known, the complete architecture of a class C GPCR and the mechanism of interdomain coupling during receptor activation are unclear. By screening a mutagenesis library of the human class C sweet taste receptor subunit T1R2, we enhanced surface expression and identified a dibasic intracellular retention motif that modulates surface expression and co-trafficking with its heterodimeric partner T1R3. Using a highly expressed T1R2 variant, dimerization sites along the entire subunit within all the structural domains were identified by a comprehensive mutational scan for co-trafficking with T1R3 in human cells. The data further reveal that the C terminus of the extracellular cysteine-rich domain needs to be properly folded for T1R3 dimerization and co-trafficking, but not for surface expression of T1R2 alone. These results guided the modeling of the T1R2–T1R3 dimer in living cells, which predicts a twisted arrangement of domains around the central axis, and a continuous folded structure between transmembrane domain loops and the cysteine-rich domains. These insights have implications for how conformational changes between domains are coupled within class C GPCRs..
8. Shingo Takai, Yu Watanabe, Keisuke Sanematsu, Ryusuke Yoshida, Robert F. Margolskee, Peihua Jiang, Ikiru Atsuta, Kiyoshi Koyano, Yuzo Ninomiya, Noriatsu Shigemura, Effects of insulin signaling on mouse taste cell proliferation, PloS one, 10.1371/journal.pone.0225190, 14, 11, 2019.01, Expression of insulin and its receptor (IR) in rodent taste cells has been proposed, but exactly which types of taste cells express IR and the function of insulin signaling in taste organ have yet to be determined. In this study, we analyzed expression of IR mRNA and protein in mouse taste bud cells in vivo and explored its function ex vivo in organoids, using RT-PCR, immunohistochemistry, and quantitative PCR. In mouse taste tissue, IR was expressed broadly in taste buds, including in type II and III taste cells. With using 3-D taste bud organoids, we found insulin in the culture medium significantly decreased the number of taste cell and mRNA expression levels of many taste cell genes, including nucleoside triphosphate diphosphohydrolase-2 (NTPDase2), Tas1R3 (T1R3), gustducin, carbonic anhydrase 4 (CA4), glucose transporter-8 (GLUT8), and sodium-glucose cotransporter-1 (SGLT1) in a concentration-dependent manner. Rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR) signaling, diminished insulin’s effects and increase taste cell generation. Altogether, circulating insulin might be an important regulator of taste cell growth and/or proliferation via activation of the mTOR pathway..
9. Keisuke Sanematsu, Yuki Nakamura, Masatoshi Nomura, Noriatsu Shigemura, Yuzo Ninomiya, Diurnal variation of sweet taste recognition thresholds is absent in overweight and obese humans, Nutrients, 10.3390/nu10030297, 10, 3, 2018.03, Sweet taste thresholds are positively related to plasma leptin levels in normal weight humans: both show parallel diurnal variations and associations with postprandial glucose and insulin rises. Here, we tested whether this relationship also exists in overweight and obese (OW/Ob) individuals with hyperleptinemia. We tested 36 Japanese OW/Ob subjects (body mass index (BMI) > 25 kg/m2 ) for recognition thresholds for various taste stimuli at seven different time points from 8:00 a.m. to 10:00 p.m. using the staircase methodology, and measured plasma leptin, insulin, and blood glucose levels before each taste threshold measurement. We also used the homeostatic model assessment of insulin resistance (HOMA-IR) to evaluate insulin resistance. The results demonstrated that, unlike normal weight subjects, OW/Ob subjects showed no significant diurnal variations in the recognition thresholds for sweet stimuli but exhibited negative associations between the diurnal variations of both leptin and sweet recognition thresholds and the HOMA-IR scores. These findings suggest that in OW/Ob subjects, the basal leptin levels (~20 ng/mL) may already exceed leptin’s effective concentration for the modulation of sweet sensitivity and that this leptin resistance-based attenuation of the diurnal variations of the sweet taste recognition thresholds may also be indirectly linked to insulin resistance in OW/Ob subjects..
10. Ryusuke Yoshida, Shingo Takai, Keisuke Sanematsu, Robert F. Margolskee, Noriatsu Shigemura, Yuzo Ninomiya, Bitter Taste Responses of Gustducin-positive Taste Cells in Mouse Fungiform and Circumvallate Papillae, Neuroscience, 10.1016/j.neuroscience.2017.10.047, 369, 29-39, 2018.01, Bitter taste serves as an important signal for potentially poisonous compounds in foods to avoid their ingestion. Thousands of compounds are estimated to taste bitter and presumed to activate taste receptor cells expressing bitter taste receptors (Tas2rs) and coupled transduction components including gustducin, phospholipase Cβ2 (PLCβ2) and transient receptor potential channel M5 (TRPM5). Indeed, some gustducin-positive taste cells have been shown to respond to bitter compounds. However, there has been no systematic characterization of their response properties to multiple bitter compounds and the role of transduction molecules in these cells. In this study, we investigated bitter taste responses of gustducin-positive taste cells in situ in mouse fungiform (anterior tongue) and circumvallate (posterior tongue) papillae using transgenic mice expressing green fluorescent protein in gustducin-positive cells. The overall response profile of gustducin-positive taste cells to multiple bitter compounds (quinine, denatonium, cyclohexamide, caffeine, sucrose octaacetate, tetraethylammonium, phenylthiourea, L-phenylalanine, MgSO4, and high concentration of saccharin) was not significantly different between fungiform and circumvallate papillae. These bitter-sensitive taste cells were classified into several groups according to their responsiveness to multiple bitter compounds. Bitter responses of gustducin-positive taste cells were significantly suppressed by inhibitors of TRPM5 or PLCβ2. In contrast, several bitter inhibitors did not show any effect on bitter responses of taste cells. These results indicate that bitter-sensitive taste cells display heterogeneous responses and that TRPM5 and PLCβ2 are indispensable for eliciting bitter taste responses of gustducin-positive taste cells..
11. Ryusuke Yoshida, Misa Shin, Keiko Yasumatsu, Shingo Takai, Mayuko Inoue, Noriatsu Shigemura, Soichi Takiguchi, Seiji Nakamura, Yuzo Ninomiya, The role of cholecystokinin in peripheral taste signaling in mice, Frontiers in Physiology, 10.3389/fphys.2017.00866, 8, OCT, 2017.10, Cholecystokinin (CCK) is a gut hormone released from enteroendocrine cells. CCK functions as an anorexigenic factor by acting on CCK receptors expressed on the vagal afferent nerve and hypothalamus with a synergistic interaction between leptin. In the gut, tastants such as amino acids and bitter compounds stimulate CCK release from enteroendocrine cells via activation of taste transduction pathways. CCK is also expressed in taste buds, suggesting potential roles of CCK in taste signaling in the peripheral taste organ. In the present study, we focused on the function of CCK in the initial responses to taste stimulation. CCK was coexpressed with type II taste cell markers such as Ga-gustducin, phospholipase Cß2, and transient receptor potential channel M5. Furthermore, a small subset (~30%) of CCK-expressing taste cells expressed a sweet/umami taste receptor component, taste receptor type 1 member 3, in taste buds. Because type II taste cells are sweet, umami or bitter taste cells, the majority of CCK-expressing taste cells may be bitter taste cells. CCK-A and -B receptors were expressed in both taste cells and gustatory neurons. CCK receptor knockout mice showed reduced neural responses to bitter compounds compared with wild-type mice. Consistently, intravenous injection of CCK-Ar antagonist lorglumide selectively suppressed gustatory nerve responses to bitter compounds. Intravenous injection of CCK-8 transiently increased gustatory nerve activities in a dose-dependent manner whereas administration of CCK-8 did not affect activities of bitter-sensitive taste cells. Collectively, CCK may be a functionally important neurotransmitter or neuromodulator to activate bitter nerve fibers in peripheral taste tissues..
12. Keisuke Sanematsu, Noriatsu Shigemura, Yuzo Ninomiya, Binding properties between human sweet receptor and sweet-inhibitor, gymnemic acids, journal of oral biosciences, 10.1016/j.job.2017.05.004, 59, 3, 127-130, 2017.08, Background Gymnemic acids, triterpene glycosides, are known to act as human-specific sweet inhibitors. The long-lasting effect of gymnemic acids is diminished by γ-cyclodextrin. Here, we focus on the molecular mechanisms underlying the interaction between gymnemic acids and sweet taste receptor and/or γ-cyclodextrin by a sweet taste receptor assay in transiently transfected HEK293 cells. Highlight Application of gymnemic acids inhibited intracellular calcium responses to sweet compounds in HEK293 cells expressing human TAS1R2+TAS1R3 but not in those expressing the mouse sweet receptor Tas1r2+Tas1r3 after application of gymnemic acids. The effect of gymnemic acids was reduced after rinsing cells with γ-cyclodextrin. Based on species-specific sensitivities to gymnemic acids, we showed that the transmembrane domain of hTAS1R3 is involved in the sensitivity to gymnemic acids. Point mutation analysis in the transmembrane domain of hTAS1R3 revealed that gymnemic acids shared the same binding pocket with another sweet inhibitor, lactisole. Sensitivity to sweet compounds was also reduced by mixtures of glucuronic acid, a common gymnemic acid. In our molecular models, gymnemic acids interacted with a binding site formed in the transmembrane domain of hTAS1R3. Conclusion Gymnemic acids inhibit sweet responses in humans through an interaction between the glucuronosyl group of gymnemic acids and the transmembrane domain of hTAS1R3. Our molecular model provides a foundation for the development of taste modifiers..
13. Masafumi Jyotaki, Keisuke Sanematsu, Noriatsu Shigemura, Ryusuke Yoshida, Yuzo Ninomiya, Leptin suppresses sweet taste responses of enteroendocrine STC-1 cells, Neuroscience, 10.1016/j.neuroscience.2016.06.036, 332, 76-87, 2016.09, Leptin is an important hormone that regulates food intake and energy homeostasis by acting on central and peripheral targets. In the gustatory system, leptin is known to selectively suppress sweet responses by inhibiting the activation of sweet sensitive taste cells. Sweet taste receptor (T1R2 + T1R3) is also expressed in gut enteroendocrine cells and contributes to nutrient sensing, hormone release and glucose absorption. Because of the similarities in expression patterns between enteroendocrine and taste receptor cells, we hypothesized that they may also share similar mechanisms used to modify/regulate the sweet responsiveness of these cells by leptin. Here, we used mouse enteroendocrine cell line STC-1 and examined potential effect of leptin on Ca2+ responses of STC-1 cells to various taste compounds. Ca2+ responses to sweet compounds in STC-1 cells were suppressed by a rodent T1R3 inhibitor gurmarin, suggesting the involvement of T1R3-dependent receptors in detection of sweet compounds. Responses to sweet substances were suppressed by ⩾1 ng/ml leptin without affecting responses to bitter, umami and salty compounds. This effect was inhibited by a leptin antagonist (mutant L39A/D40A/F41A) and by ATP gated K+ (KATP) channel closer glibenclamide, suggesting that leptin affects sweet taste responses of enteroendocrine cells via activation of leptin receptor and KATP channel expressed in these cells. Moreover, leptin selectively inhibited sweet-induced but not bitter-induced glucagon-like peptide-1 (GLP-1) secretion from STC-1 cells. These results suggest that leptin modulates sweet taste responses of enteroendocrine cells to regulate nutrient sensing, hormone release and glucose absorption in the gut..
14. Sunil K. Sukumarana, Karen K. Yeea, Shusuke Iwatab, Ramana Kothaa, Roberto Quezada-Calvillo, Buford L. Nichols, Sankar Mohan, B. Mario Pinto, Noriatsu Shigemura, Yuzo Ninomiya, Robert F. Margolskee, Taste cell-expressed α-glucosidase enzymes contribute to gustatory responses to disaccharides, Proceedings of the National Academy of Sciences of the United States of America, 10.1073/pnas.1520843113, 113, 21, 6035-6040, 2016.05, The primary sweet sensor in mammalian taste cells for sugars and noncaloric sweeteners is the heteromeric combination of type 1 taste receptors 2 and 3 (T1R2+T1R3, encoded by Tas1r2 and Tas1r3 genes). However, in the absence of T1R2+T1R3 (e.g., in Tas1r3 KO mice), animals still respond to sugars, arguing for the presence of T1Rindependent detection mechanism(s). Our previous findings that several glucose transporters (GLUTs), sodium glucose cotransporter 1 (SGLT1), and the ATP-gated K+ (KATP ) metabolic sensor are preferentially expressed in the same taste cells with T1R3 provides a potential explanation for the T1R-independent detection of sugars: sweet-responsive taste cells that respond to sugars and sweeteners may contain a T1R-dependent (T1R2+T1R3) sweet-sensing pathway for detecting sugars and noncaloric sweeteners, as well as a T1Rindependent (GLUTs, SGLT1, KATP ) pathway for detecting monosaccharides. However, the T1R-independent pathway would not explain responses to disaccharide and oligomeric sugars, such as sucrose, maltose, and maltotriose, which are not substrates for GLUTs or SGLT1. Using RT-PCR, quantitative PCR, in situ hybridization, and immunohistochemistry, we found that taste cells express multiple α-glycosidases (e.g., amylase and neutral α glucosidase C) and so-called intestinal "brush border" disaccharide-hydrolyzing enzymes (e.g., maltase-glucoamylase and sucrase-isomaltase). Treating the tongue with inhibitors of disaccharidases specifically decreased gustatory nerve responses to disaccharides, but not to monosaccharides or noncaloric sweeteners, indicating that lingual disaccharidases are functional. These taste cell-expressed enzymes may locally break down dietary disaccharides and starch hydrolysis products into monosaccharides that could serve as substrates for the T1R-independent sugar sensing pathways..
15. Keisuke Sanematsu, Masayuki Kitagawa, Ryusuke Yoshida, S Nirasawa, Noriatsu Shigemura, Yuzo Ninomiya, Intracellular acidification is required for full activation of the sweet taste receptor by miraculin., Sci Rep., 6, 22807, 2016.03.
16. Noriatsu Shigemura, Yuzo Ninomiya, Recent Advances in Molecular Mechanisms of Taste Signaling and Modifying., Int Rev Cell Mol Biol., 323, 71-106, 2016.02.
17. Ryusuke Yoshida, Kenshi Noguchi, Noriatsu Shigemura, Masafumi Jyotaki, Ichiro Takahashi, Robert F Margolskee, Yuzo Ninomiya, Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds., Diabetes., 64, 11, 3751-3762, 2015.06.
18. Noriatsu Shigemura, Modulation of Taste Responsiveness by Angiotensin II., Food Science and Technology Research, 21 , 6, 757-764, 2015.06.
19. Noriatsu Shigemura, Angiotensin II and taste sensitivity., Japanese Dental Science Review, 51, 2, 51-8, 2015.05.
20. Shingo Takai, Keiko Yasumatsu, Mayuko Inoue, Shusuke Iwata, Ryusuke Yoshida, Noriatsu Shigemura, Yuchio Yanagawa, Daniel J. Drucker, Robert F Margolskee, Yuzo Ninomiya, Glucagon-like peptide-1 is specifically involved in sweet taste transmission., FASEB J., in press, 2015.02.
21. Mayu Niki, Masafumi Jyotaki, Ryusuke Yoshida, Keiko Yasumatsu, Noriatsu Shigemura, Nicholas V. DiPatrizio, Daniele Piomelli, Yuzo Ninomiya, Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice., J Physiol., in press, 2015.02.
22. Keisuke Sanematsu, Ryusuke Yoshida, Noriatsu Shigemura, Yuzo Ninomiya, Structure, function, and signaling of taste G-protein-coupled receptors., Curr Pharm Biotechnol., 15, 10, 951-61, 2014.10.
23. Keisuke Sanematsu, Yuko Kusakabe, Noriatsu Shigemura, Takatsugu Hirokawa, Seiji Nakamura, Toshiaki Imoto, Yuzo Ninomiya, Molecular mechanisms for sweet-suppressing effect of gymnemic acids., J Biol Chem., 289, 37, 25711-20, 2014.09.
24. Noriatsu Shigemura, Shusuke Iwata, Keiko Yasumatsu, Tadahiro Ohkuri, Nao Horio, Keisuke Sanematsu, Ryusuke Yoshida, Robert F Margolskee, Yuzo Ninomiya, Angiotensin II modulates salty and sweet taste sensitivities., J Neurosci., 33, 15, 6267-6277, 2013.04, アンジオテンシンIIは、視床下部、副腎や血管などに発現するAT1受容体を介して、血圧や体内Na+濃度を調節する鍵ホルモンとして知られている。我々は、このアンジオテンシンIIが末梢の味覚器にも働き、塩味感受性を低下させ NaCl溶液の摂取量を増加させること、さらに甘味感受性を増強することで糖分摂取にも影響することを明らかにした。この“味覚を介したNa+/糖ホメオスタシス維持機構”のさらなる解明は、高血圧や肥満・糖尿病などの生活習慣病に対する新たな予防・治療法の開発”に繋がることが期待される。.
25. Yoshida R, Niki M, Jyotaki M, Sanematsu K, Shigemura N, Ninomiya Y., Modulation of sweet responses of taste receptor cells., Semin Cell Dev Biol., S1084-9521, (12), 2012.08.
26. Cartoni C, Yasumatsu K, Ohkuri T, Shigemura N, Yoshida R, Godinot N, le Coutre J, Ninomiya Y, Damak S. , Taste preference for fatty acids is mediated by GPR40 and GPR120., J Neurosci. , 30, (25), 8376-82. , 2010.06.
27. Jyotaki M, Shigemura N, Ninomiya Y., Modulation of sweet taste sensitivity by orexigenic and anorexigenic factors., Endocr J., 2010.04.
28. Yoshida R, Ohkuri T, Jyotaki M, Yasuo T, Horio N, Yasumatsu K, Sanematsu K, Shigemura N, Yamamoto T, Margolskee RF, Ninomiya Y., Endocannabinoids selectively enhance sweet taste., Proc Natl Acad Sci U S A., 107(2):935-9., 2010.01.
29. Horio N, Jyotaki M, Yoshida R, Sanematsu K, Shigemura N, Ninomiya Y., New frontiers in gut nutrient sensor research: nutrient sensors in the gastrointestinal tract: modulation of sweet taste sensitivity by leptin., J Pharmacol Sci., 112(1):8-12., 2010.01.
30. Yasumatsu K, Ohkuri T, Sanematsu K, Shigemura N, Katsukawa H, Sako N, Ninomiya Y., Genetically-increased taste cell population with G(alpha)-gustducin-coupled sweet receptors is associated with increase of gurmarin-sensitive taste nerve fibers in mice., BMC Neurosci., 10:152., 2009.12.
31. Yoshida R, Miyauchi A, Yasuo T, Jyotaki M, Murata Y, Yasumatsu K, Shigemura N, Yanagawa Y, Obata K, Ueno H, Margolskee RF, Ninomiya Y., Discrimination of taste qualities among mouse fungiform taste bud cells., J Physiol., 587(Pt 18):4425-39., 2009.09.
32. Shigemura N, Shirosaki S, Ohkuri T, Sanematsu K, Islam AA, Ogiwara Y, Kawai M, Yoshida R, Ninomiya Y., Variation in umami perception and in candidate genes for the umami receptor in mice and humans.
, Am J Clin Nutr. , 90(3):764S-769S., 2009.09.
33. Shigemura N, Shirosaki S, Sanematsu K, Yoshida R, Ninomiya Y., Genetic and molecular basis of individual differences in human umami taste perception., PLoS One., 4(8):e6717., 2009.08.
34. Yoshida R, Yasumatsu K, Shirosaki S, Jyotaki M, Horio N, Murata Y, Shigemura N, Nakashima K, Ninomiya Y., Multiple receptor systems for umami taste in mice., Ann N Y Acad Sci., 1170:51-4., 2009.07.
35. Sanematsu K, Horio N, Murata Y, Yoshida R, Ohkuri T, Shigemura N, Ninomiya Y., Modulation and transmission of sweet taste information for energy homeostasis., Ann N Y Acad Sci., 1170:102-6., 2009.07.
36. Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Kojima I., Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion., PLoS One., 4(4):e5106, 2009.04.
37. Yoshida R, Horio N, Murata Y, Yasumatsu K, Shigemura N, Ninomiya Y., NaCl responsive taste cells in the mouse fungiform taste buds., Neuroscience., 159(2):795-803., 2009.03.
38. Nakamura Y, Sanematsu K, Ohta R, Shirosaki S, Koyano K, Nonaka K, Shigemura N, Ninomiya Y., Diurnal variation of human sweet taste recognition thresholds is correlated with plasma leptin levels., Diabetes. , 57(10):2661-5., 2008.10.
39. Shigemura, N., Nakao, K., Yasuo, T., Murata, Y., Yasumatsu, K., Nakashima, A., Katsukawa, H., Sako, N., Ninomiya, Y. , Gurmarin sensitivity of sweet taste responses is associated with co-expression patterns of T1r2, T1r3, and gustducin. , Biochem. Biophys. Res. Commun., 367, 356-363 , 2008.03.
40. Shigemura, N., Ohkuri, T., Sadamitsu, C., Yasumatsu, K., Yoshida, R., Beauchamp, G.K., Bachmanov, A.A., Ninomiya, Y. , Amiloride-sensitive NaCl taste responses are associated with genetic variation of ENaC α subunit in mice., Am. J. Physiol. Regul Integr. Comp. Physiol., 294, R66-R75 , 2008.01.
41. Yasumatsu, K., Kusuhara, Y., Shigemura, N., Ninomiya, Y. , Recovery of two independent sweet taste systems during regeneration of the mouse chorda tympani nerve after nerve crush. , Eur. J. Neurosci., 26, 1521-1529, 2007.09.
42. Yoshida R, Shigemura N, Sanematsu K, Yasumatsu K, Ishizuka S, Ninomiya Y., Taste responsiveness of fungiform taste cells with action potentials. , J Neurophysiol. , 96(6):3088-95., 2006.12.
43. Ohkuri T, Yasumatsu K, Shigemura N, Yoshida R, Ninomiya Y. , Amiloride inhibition on NaCl responses of the Chorda Tympani nerve in two 129 substrains of mice, 129P3/J and 129X1/SvJ. , Chem Senses, 31(6):565-72. , 2006.07.
44. Damak S, Rong M, Yasumatsu K, Kokrashvili Z, Perez CA, Shigemura N, Yoshida R, Mosinger B Jr, Glendinning JI, Ninomiya Y, Margolskee RF., Trpm5 null mice respond to bitter, sweet, and umami compounds. , Chem Senses, 31(3):253-64. , 2006.03.
45. Talavera K, Yasumatsu K, Voet T, Droogmans G, Shigemura N, Ninomiya Y, Margolskee RF, Nilius B., Heat-activation of the taste channel TRPM5 underlies thermal sensitivity to sweet., Nature, 438(7070):1022-5, 2005.12.
46. Shigemura N, Islam AA, Sadamitsu C, Yoshida R, Yasumatsu K, Ninomiya Y., Expression of amiloride-sensitive epithelial sodium channels in mouse taste cells after chorda tympani nerve crush., Chemical Senses, 10.1093/chemse/bji046, 30, 6, 531-538, 30(6):531-8, 2005.07.
47. Sanematsu K, Yasumatsu K, Yoshida R, Shigemura N, Ninomiya Y., Mouse strain differences in Gurmarin-sensitivity of sweet taste responses are not associated with polymorphisms of the sweet receptor gene, Tas1r3., Chemical Senses., 10.1093/chemse/bji041, 30, 6, 491-496, 30(6):491-6, 2005.06.
48. Yasumatsu K, Shigemura N, Yoshida R, Ninomiya Y., Recovery of Salt Taste Responses and PGP 9.5 Immunoreactive Taste Bud Cells during Regeneration of the Mouse Chorda Tympani Nerve., Chemical Senses, 10.1093/chemse/bjh114, 30, I62-i63, Suppl 1:i62-i63, 2005.01.
49. Shigemura, N., Yasumatsu, K., Yoshida, R., Sako, N., Katsukawa, H., Nakashima K., Imoto, T., Ninomiya, Y., The role of the dpa locus in mice. Jan;30 (2005), Chemical Senses, 10.1093/chemse/bjh125, 30, I84-i85, Suppl 1:i84-i85, 2005.01.
50. Shigemura N, Ohta R, Kusakabe Y, Miura H, Hino A, Koyano K, Nakashima K, Ninomiya Y., Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structures., Endocrinology, 10.1210/en.2003-0602, 145, 2, 839-847, 2003.10.
51. Ohta R, Shigemura N, Sasamoto K, Koyano K, Ninomiya Y., Conditioned taste aversion learning in leptin-receptor-deficient db/db mice., Neurobiol Learn Mem., 10.1016/S1074-7427(03)00046-7, 80, 2, 105-112, 80(2):105-12, 2003.09.
52. Shigemura N, Miura H, Kusakabe Y, Hino A, Ninomiya Y., Expression of leptin receptor (Ob-R) isoforms and signal transducers and activators of transcription (STATs) mRNAs in the mouse taste buds., Arch Histol Cytol., 10.1679/aohc.66.253, 66, 3, 253-260, 66(3):253-60., 2003.08.
53. Murata Y, Nakashima K, Yamada A, Shigemura N, Sasamoto K, Ninomiya Y, Gurmarin suppression of licking responses to sweetener-quinine mixtures in C57BL mice, CHEMICAL SENSES, 10.1093/chemse/28.3.237, 28, 3, 237-243, 28 (3): 237-243, 2003.03.
54. Ion channels and second messengers involved in transduction and modulation of sweet taste in mouse taste cells

Sugimoto K, Shigemura N, Yasumatsu K, Ohta R, Nakashima K, Kawai K, Ninomiya Y

74 (7): 1141-1151 JUL 2002

Leptin, a hormone released from the adipose tissue, inhibits food intake and increases energy expenditure. We have found a novel function of leptin as a modulator of sweet taste sensitivity in mice. In lean normal mice, the gustatory nerve responses to sweet stimuli were selectively suppressed depending on plasma leptin level after an intraperitoneal injection of recombinant leptin. Patch-clamp studies using isolated taste cells of lean mice showed that extracellular leptin enhanced K+ currents of sweet-responsive taste cells, which led to membrane hyperpolarization and a reduction of sweetener-induced depolarization. Reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization analyses demonstrated specific expression of mRNA of the long-form functional leptin receptor (Ob-Rb) in taste tissue and cells of lean mice. The genetically diabetic db/db mice, which have defects in Ob-Rb, demonstrated neither a suppression of gustatory neural responses to sweeteners nor an increment of whole-cell K+ conductance of taste cells even with high doses of leptin. These results suggest that Ob-Rb is specifically expressed in sweet-responsive taste cells of lean mice and that leptin suppresses sweetener-induced depolarization via activation of K+ channels, leading to a decrease in impulses of sweet-best fibers. The enhanced sweet responses of db/db mice may result from the lack of inhibitory modulation by leptin..
55. Ninomiya, Y., Shigemura, N., Yasumatsu, K., Ohta, R., Sugimoto, K., Nakashima, K. and Lindemann, B., Leptin and sweet taste., Vitam. Horm., 10.1016/S0083-6729(02)64007-5, 64, 221-248, 64: 221-247, 2002.05.
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