The sweet taste receptor, glucose transporters, and the ATP-sensitive K+ (KATP) channel: sugar sensing for the regulation of energy homeostasis

Sugar detection in the oral cavity does not solely depend on the TAS1R2 + TAS1R3 sweet receptor. Similar to gut, pancreas, and hypothalamic neurons, in the tongue glucose transporters and ATP-sensitive K+ (KATP) channels are also involved in sugar detection. Among them, the KATP channel is the target for the antiobesity hormone leptin, which inhibits sugar-sensitive cells such as sweet taste cells, pancreatic β-cells, and hypothalamic orexigenic neurons. Sugar signals from the taste organ elicit cephalic-phase insulin release, and those from the gut contribute to sweet preference for caloric sugars. All of these systems are indispensable for maintaining energy homeostasis. Thus, an exquisite system for sugar detection/signaling to regulate energy homeostasis exists in our body

Phosphatidylinositol‐3 kinase mediates the sweet suppressive effect of leptin in mouse taste cells

Leptin is known to selectively suppress neural and taste cell responses to sweet compounds. The sweet suppressive effect of leptin is mediated by the leptin receptor Ob‐Rb, and the ATP‐gated K+ (KATP) channel expressed in some sweet‐sensitive, taste receptor family 1 member 3 (T1R3)‐positive taste cells. However, the intracellular transduction pathway connecting Ob‐Rb to KATP channel remains unknown. Here we report that phosphoinositide 3‐kinase (PI3K) mediates leptin's suppression of sweet responses in T1R3‐positive taste cells. In in situ taste cell recording, systemically administrated leptin suppressed taste cell responses to sucrose in T1R3‐positive taste cells. Such leptin's suppression of sucrose responses was impaired by co‐administration of PI3K inhibitors (wortmannin or LY294002). In contrast, co‐administration of signal transducer and activator of transcription 3 inhibitor (Stattic) or Src homology region 2 domain‐containing phosphatase‐2 inhibitor (SHP099) had no effect on leptin's suppression of sucrose responses, although signal transducer and activator of transcription 3 and Src homology region 2 domain‐containing phosphatase‐2 were expressed in T1R3‐positive taste cells. In peeled tongue epithelium, phosphatidylinositol (3,4,5)‐trisphosphate production and phosphorylation of AKT by leptin were immunohistochemically detected in some T1R3‐positive taste cells but not in glutamate decarboxylase 67‐positive taste cells. Leptin‐induced phosphatidylinositol (3,4,5)‐trisphosphate production was suppressed by LY294002. Thus, leptin suppresses sweet responses of T1R3‐positive taste cells by activation of Ob‐Rb–PI3K–KATP channel pathway

Effects of Bitter Receptor Antagonists on Behavioral Lick Responses of Mice

Bitter taste receptors TAS2Rs detect noxious compounds in the oral cavity. Recent heterologous expression studies reported that some compounds function as antagonists for human TAS2Rs. For examples, amino acid derivatives such as γ-aminobutyric acid (GABA) and Nα,Nα-bis(carboxymethyl)-L-Lysine (BCML) blocked responses to quinine mediated by human TAS2R4. Probenecid inhibited responses to phenylthiocarbamide mediated by human TAS2R38. In this study, we investigated the effects of these human bitter receptor antagonists on behavioral lick responses of mice to elucidate whether these compounds also function as bitter taste blockers. In short-term (10 s) lick tests, concentration-dependent lick responses to bitter compounds (quinine-HCl, denatonium and phenylthiourea) were not affected by the addition of GABA or BCML. Probenecid reduced aversive lick responses to denatonium and phenylthiourea but not to quinine-HCl. In addition, taste cell responses to phenylthiourea were inhibited by probenecid. These results suggest some bitter antagonists of human TAS2Rs can work for bitter sense of mouse

Musculoskeletal Estimation Using Inertial Measurement Units and Single Video Image

International audienceWe address the problem of estimating the physical burden of a human body. This translates to monitor and estimate muscle tension and joint reaction forces of a mus-culoskeletal model in real-time. The system should minimize the discomfort generating by any sensors that needs to be fixed on the user. Our system combines a 3D pose estimation from vision and IMU sensors. We aim to minimize the number of IMU fixed to the subject while compensating the remaining lack of information with vision

The Effects of Mutual Interaction of Orexin-A and Glucagon-Like Peptide-1 on Reflex Swallowing Induced by SLN Afferents in Rats

(1) Background: Our previous studies revealed that orexin-A, an appetite-increasing peptide, suppressed reflex swallowing via the commissural part of the nucleus tractus solitarius (cNTS), and that glucagon-like peptide-1 (GLP-1), an appetite-reducing peptide, also suppressed reflex swallowing via the medial nucleus of the NTS (mNTS). In this study, we examined the mutual interaction between orexin-A and GLP-1 in reflex swallowing. (2) Methods: Sprague-Dawley rats under urethane-chloralose anesthesia were used. Swallowing was induced by electrical stimulation of the superior laryngeal nerve (SLN) and was identified by the electromyographic (EMG) signals obtained from the mylohyoid muscle. (3) Results: The injection of GLP-1 (20 pmol) into the mNTS reduced the swallowing frequency and extended the latency of the first swallow. These suppressive effects of GLP-1 were not observed after the fourth ventricular administration of orexin-A. After the injection of an orexin-1 receptor antagonist (SB334867) into the cNTS, an ineffective dose of GLP-1 (6 pmol) into the mNTS suppressed reflex swallowing. Similarly, the suppressive effects of orexin-A (1 nmol) were not observed after the injection of GLP-1 (6 pmol) into the mNTS. After the administration of a GLP-1 receptor antagonist (exendin-4(5-39)), an ineffective dose of orexin-A (0.3 nmol) suppressed reflex swallowing. (4) Conclusions: The presence of reciprocal inhibitory connections between GLP-1 receptive neurons and orexin-A receptive neurons in the NTS was strongly suggested

Bitter Taste Responses of Gustducin-positive Taste Cells in Mouse Fungiform and Circumvallate Papillae

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

Control of the glass-liquid transition temperature in YBa2Cu3O7-x films

Magnetic field dependences of the glass-liquid transition temperature (Tg) were studied in YBa2Cu3O7−x films containing various types of nanoinclusions. The vortex configuration entangled or straight and pinning strength for each vortex are crucial to the behaviors of Tg. c-axis correlated pinning centers optimize these factors and achieve the upper limit of Tg, which is determined by loss of line tension of vortices, if they are elongated through a thickness of a sample. By optimizing pinning centers, critical temperature, and a matching field, a Tg value of 77 K can be obtained in YBa2Cu3O7−x in a magnetic field as high as 27 T

Nanostructures and flux pinning properties in YBa2Cu3O7−y thin films with double perovskite Ba2LuNbO6 nanorods

Double perovskite Ba2LuNbO6 (BLNO)-doped YBa2Cu3O7−y (YBCO) thin films are fabricated on a SrTiO3 (001) substrate by pulsed laser deposition, and their nanostructures are characterized by transmission electron microscopy and scanning transmission electron microscopy. Cross-sectional observations and elemental mapping reveal that BLNO self-assembles during thin film deposition, and consequently, nanorods extending straight from the substrate to the surface are formed in the YBCO thin films. It is confirmed that stacking faults perpendicular to the growth direction disturb the formation of BLNO nanorods. Strain maps extracted by geometric phase analysis reveal that the tensile strain occurs in the YBCO matrix around the BLNO nanorods. Misfit dislocations are periodically introduced at the interface between the nanorod and the matrix, which results in the inhomogeneous strain of YBCO around the BLNO nanorods. The superconducting properties of the YBCO + BLNO thin films are compared with those of other previously reported YBCO thin films with normal perovskite and double perovskite nanorods

Superwind-Driven Intense H_2 Emission in NGC 6240

We have performed a long-slit K band spectroscopic observation of the luminous infrared galaxy NGC 6240. The peak position of the H_2 v=1-0 S(1) emission in the slit is located ~0.3" - 0.4" north of the southern nucleus. It is almost the midpoint between the southern nucleus and the peak position of the ^12CO J=1-0 emission. Based on the line-ratio analyses, we suggest the excitation mechanism of H_2 is pure thermal at most positions. In the southern region we find the following three velocity components in the H_2 emission: the blueshifted shell component (~-250 km s^-1 with respect to V_sys) which is recognized as a distinct C-shape distortion in the velocity field around the southern nucleus, the high-velocity blueshifted ``wing'' component (~-1000 km s^-1 with respect to V_sys), and the component indicating possible line splitting of ~500 km s^-1. The latter two components are extended to the south from the southern nucleus. We show that the kinematic properties of these three components can be reproduced by expanding motion of a shell-like structure around the southern nucleus. The offset peak position of the H_2 emission can be understood if we assume that the shell expanding to the north interacts with the extragalactic molecular gas. At the interface between the shell and the molecular gas concentration the cloud-crushing mechanism proposed by Cowie et al. (1981) may work efficiently, and the intense H_2 emission is thus expected there. All these findings lead us to propose a model that the most H_2 emission is attributed to the shock excitation driven by the superwind activity of the southern nucleus.Comment: 33 pages, 9 figures, accepted for publication in PAS