Could hop-derived bitter compounds improve glucose homeostasis by stimulating the secretion of GLP-1?

Hops (Humulus lupulus L.) is by far the greatest contributors to the bitter property of beer. Over the past years, a large body of evidence demonstrated the presence of taste receptors in different locations of the oral cavity. In addition to the taste buds of the tongue, cells expressing these receptors have been identified in olfactory bulbs, respiratory and gastrointestinal tract. In the gut, the attention was mainly directed to sweet Taste Receptor (T1R) and bitter Taste Receptor (T2R) receptors. In particular, T2R has shown to modulate secretion of different gut hormones, mainly Glucagon-like Peptide 1 (GLP-1), which are involved in the regulation of glucose homeostasis and the control of gut motility, thereby increasing the sense of satiety. Scientific interest in the activity of bitter taste receptors emerges because of their wide distribution in the human species and the large range of natural substances that interact with them. Beer, whose alcohol content is lower than in other common alcoholic beverages, contains a considerable amount of bitter compounds and current scientific evidence shows a direct effect of beer compounds on glucose homeostasis. The purpose of this paper is to review the available literature data in order to substantiate the novel hypothesis of a possible direct effect of hop-derived bitter compounds on secretion of GLP-1, through the activation of T2R, with consequent improvement of glucose homeostasis.

DNA-mediated self-assembly of taste cells and neurons for taste signal transmission.

Cells can communicate with one another through physical connections and chemical signaling, activating various signaling pathways that can affect cellular functions and behaviors. In taste buds, taste cells transmit taste information to neurons via paracrine signaling. However, no previous studies have reported the in vitro co-culture of taste and neuronal cells, which allows us to monitor intercellular communications and better understand the mechanism of taste perception. Here, we introduce the first investigation on the proximate assembly and co-culture of taste cells and neurons to monitor the intercellular transmission of taste signals. Taste cells and neurons are placed closely using a pair of single-stranded oligonucleotides conjugated with polyethylene glycol and a phospholipid. Complementary oligonucleotide conjugates are anchored into the cellular membrane of neonatal taste cells and embryonic hippocampal neuronal cells, respectively, and then the cells are self-assembled into a functional multicellular unit for taste perception. Treatment of the assembled cells with a bitter tastant generates the sequential influx of calcium ions into the cytoplasm in taste cells and then in neuronal cells. Our work demonstrates that the cellular self-assembly is critical for efficient taste signal transduction, which can be used as a promising platform to construct cell-based biosensors for taste sensing.

Zizyphin modulates calcium signalling in human taste bud cells and fat taste perception in the mouse.

Zizyphin, isolated from Zizyphus sps. leaf extracts, has been shown to modulate sugar taste perception, and the palatability of a sweet solution is increased by the addition of fatty acids. We, therefore, studied whether zizyphin also modulates fat taste perception. Zizyphin was purified from edible fruit of Zizyphus lotus L. Zizyphin-induced increases in [Ca2+ ]i in human taste bud cells (hTBC). Zizyphin shared the endoplasmic reticulum Ca2+ pool and also recruited, in part, Ca2+ from extracellular environment via the opening of store-operated Ca2+ channels. Zizyphin exerted additive actions on linoleic acid (LA)-induced increases in [Ca2+ ]i in these cells, indicating that zizyphin does not exert its action via fatty acid receptors. However, zizyphin seemed to exert, at least in part, its action via bile acid receptor Takeda-G-protein-receptor-5 in hTBC. In behavioural tests, mice exhibited preference for both LA and zizyphin. Interestingly, zizyphin increased the preference for a solution containing-LA. This study is the first evidence of the modulation of fat taste perception by zizyphin at the cellular level in hTBC. Our study might be helpful for considering the synthesis of zizyphin analogues as 'taste modifiers' with a potential in the management of obesity and lipid-mediated disorders.

Qing-Hua Granule induces GLP-1 secretion via bitter taste receptor in db/db mice.

Qing-Hua Granule (QHG), the modified formulation of a classical Chinese prescription named Gegen Qinlian Decoction, was clinically employed to treat type 2 diabetes mellitus (T2DM) through regulation of glucagon-like peptide-1 (GLP-1). However, the potential mechanism is unknown. We investigate whether QHG induces GLP-1 secretion via activation of bitter taste receptor (TAS2R) pathway in the gastrointestinal tract of db/db mice. The db/db mice were intragastrically (i.g.) administered QHG (low/medium/high dose) once daily for 8 weeks. GLP-1 secretion was evaluated. The bitter receptor signaling pathway, which regulates GLP-1 secretion, including TAS2R5 (a subtype of TAS2R), α-gustducin (Gαgust), 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase beta-2 (PLCß2), transient receptor potential cation channel subfamily M member 5 (TRPM5), was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC). The biochemical observations of ileum and pancreas tissue were detected histopathologically. Acquity Ultra Performance LCTM - Micromass ZQ 2000 (UPLC-MS) was used for the phytochemical analysis. QHG exhibited significant and dose-dependent effect on GLP-1 secretion in db/db mice, along with significant up-regulation of TAS2R5 mRNA level and activation of TAS2R pathway (p<0.05). In addition, QHG improved the histopathological structure of ileum and pancreatic tissue. Seventeen compounds were identified in QHG. In conclusion, QHG induces GLP-1 secretion in db/db mice, most likely through the bitter taste receptor pathway.

An Interesting Tour of New Research Results on Umami and Umami Compounds.

Knowledge about the fifth basic taste, the umami taste, has been investigated by many scientists in the last years and continues to gain importance. Therefore, a lot of scientific studies were conducted to explore several effects influencing the mechanism of umami, which is elicited and enhanced by defined concentrations of MSG (monosodium glutamate) and umami compounds. This paper covers the most relevant scientific literature regarding umami, its use as a flavor enhancer, and the latest umami compounds, which have been released in the last ten years. The main goal of this overview was to summarize the most important results which were related to umami as one of the five basic tastes, the umami taste receptor, the essential role of umami in a great number of physiological mechanisms, and the MSG symptom complex. Furthermore, the function of umami in the interaction of taste, aftertaste and olfactory pathways has been discussed.

Development of a model for robust and exploratory analysis of the rodent brief-access taste aversion data.

The rodent brief-access taste aversion (BATA) model is an efficient in vivo screening tool for taste assessment. A new E(max) (maximum effect attributable to the drug) model was developed and further investigated in comparison with three previously published models for analysing the rodent BATA data; the robustness of all the models was discussed. The rodent BATA data were obtained from a series of experiments conducted with a bitter reference compound, quinine hydrochloride dihydrate (QHD). A new E(max) model that could be applied to both "lick numbers" and "lick ratios" was built and three published models that used lick ratios were employed for analysing the BATA data. IC50, the concentration that inhibits 50% of the maximum lick numbers, quantified the oral aversiveness of QHD. One thousand bootstrap datasets were generated from the original data. All models were applied to estimate the confidence intervals of the IC50s without symmetric assumption. The IC50 value obtained from the new E(max) model was 0.0496 mM (95% CI 0.0297-0.0857) using the lick numbers for analysis, while an IC50 of 0.0502 mM (95% CI 0.0267-0.0859) was acquired with the lick ratios. Except one published model, the IC50 values have a similar range for the 95% CI. The new E(max) model enabled the analysis of both "lick numbers" and "lick ratios" whereas other models could only handle data presented as "lick ratios". IC50s obtained with these two types of datasets showed similarity among all models thereby justified the robustness of the new E(max) model.

The clinical effects of Synsepalum dulcificum: a review.

Synsepalum dulcificum or the "miracle fruit" is well known for its taste-modifying ability. The aim of this review was to assess the published medically beneficial as well as potential characteristics of this fruit. A search in three databases, including PubMed, ScienceDirect, and Google Scholar, was made with appropriate keywords. The resulting articles were screened in different stages based on the title, abstract, and content. A total of nine articles were included in this review. This review summarized the findings of previously published studies on the effects of miracle fruit. The main studied characteristic of the fruit was its effect on the taste receptors, resulting in the sweet sensation when substances with acidic content were ingested. This effect was shown to be related to a glycoprotein called "miraculin." Other beneficial characteristics of this fruit were its antioxidant and anticancer abilities that are due to the various amides existing in the miracle fruit. Apart from the above, the other observed effect of this fruit was its antidiabetic effect that was tested in rats. Further studies should be conducted to establish the findings. The miracle fruit can be a healthy additive due to its unique characteristics, including sour taste sensation modification as well as its antioxidant and antidiabetic effects.

Confocal microscopy of the peripheral gustatory system: comparison between healthy subjects and patients suffering from taste disorders during radiochemotherapy.

OBJECTIVES: Laser-scanning microscopy (LSM) was used to compare taste buds and epithelia of fungiform papillae of healthy subjects with those of patients suffering from taste disorders during/after radiochemotherapy (RCT). Aim of the study was to investigate effects responsible for taste loss at a microscopic level. STUDY DESIGN: Prospective study. METHODS: Data from 12 healthy subjects (mean age 52.4, SD 9.5 years) were compared with those of 12 patients (mean age 54.7, SD 8.5 years) with head and neck cancer suffering from taste disorders during RCT. Four parameters from LSM were selected for analysis: 1) distance between the pore of the taste buds of fungiform papillae and the crest of the papillary vessels; 2) epithelial cells of each taste bud at 34 mum; 3), cell density, and 4) area of the taste pore at 4 mum. These data were correlated to measures of gustatory sensitivity obtained with both the validated "taste strips" test kit and electrogustometry. RESULTS: Patients complaining from taste disorders during RCT exhibited a significant decrease of taste function assessed with both natural and electric stimuli. In these patients, we found thicker epithelia and smaller areas of the taste pores compared with healthy subjects. In 30% of those patients, no taste pores were detectable; in deeper sections, however, normal taste buds were present. CONCLUSIONS: In conclusion, in RCT patients with taste disorders, LSM indicates changes of epithelia of fungiform papilla but no changes of the taste bud structure. Damage of the chorda tympani nerve by scattered rays, direct or indirect mucotoxic effects of chemotherapeutic agents, and covering of taste pores by epithelial cells are likely reasons for taste loss during RCT.

Peptides that regulate food intake: somatostatin alters intake of amino acid-imbalanced diets and taste buds of tongue in rats.

The present studies were designed to evaluate a potential dose-dependent effect of somatostatin (SRIF) administered peripherally on intake of either a low-protein basal diet or threonine-imbalanced diet (THR-IMB), on body weight gain (DeltaBW), gut motility, and on the histology of taste buds in rats. SRIF administration had a dual effect related to its concentration, increasing the intake of THR-IMB diet at low concentration and decreasing THR-IMB diet at high concentration. During the light phase, SRIF treatment increased the intake of THR-IMB diet, suggesting that the usual anorectic effect induced by intake of THR-IMB diet was attenuated. High-dosage SRIF decreases gastrointestinal motility, which, in turn, can decrease food intake and DeltaBW. The combination of THR-IMB diet regimen and SRIF treatment also induced significant modifications on the taste buds of the tongue. The feeding response to an amino acid-imbalanced diet includes a learned aversion to the diet, and animals may use taste in establishing that aversion. Modifications of taste buds of SRIF-treated rats eating THR-IMB diet might explain the increase of imbalanced diet intake if treated rats perceive this food as less aversive.

The role of the chorda tympani nerve in the activation of the rat hypothalamic histaminergic system by leptin.

A possible pathway through which leptin activates the histaminergic system was studied using in vivo microdialysis in rats. Intraperitoneal injection of leptin (1.3 mg/kg) caused a significant increase in hypothalamic histamine release, however, its intracerebroventricular injection (10 microg/rat) did not cause any significant changes in the release. Furthermore, leptin (1.3 mg/kg) had no effect on histamine release in rats whose chorda tympani nerves, a branch of the facial nerve which mediates taste information, were transected bilaterally. These findings indicate that leptin activates the histaminergic system by the peripheral signal inputs via the chorda tympani resulting in the suppression of food intake.

Sensory evaluation of stored and rancid edible oils.

The sensory evaluation of stored and rancid edible oils is substantially influenced by tasting of the previous sample. Oil forms a film on walls of the oral cavity, modifying the access of active substances to taste receptors, and inhibiting the evaporation of volatiles to olfactory receptors. Intensities of different off-flavours decrease, while the flavour acceptancy increases. About 5-10 min after the first sensory test, the response of sensory receptors returns to the original sensitivity.

The effect of neonatal capsaicin treatment on gustatory behavior in the albino rat.

Small-diameter fibers present in gustatory peripheral nerves have historically been suspected of relaying information about the bitter quality of a taste stimulus. Neonatally injected capsaicin irreversibly destroys a proportion of unmyelinated C- and some A delta-fibers. Consummatory responses to increasing concentrations of quinine and other chemical solutions following neonatal capsaicin injection were compared to those of untreated and vehicle-injected control Sabra albino rats. Capsaicin-treated rats significantly increased their withdrawal thresholds to noxious, CO2 laser-generated heat pulses verifying treatment effectiveness. Furthermore, neonatal capsaicin treatment diminished sensitivity to pungent capsaicin solutions in mature rats. However, there were no group differences in quinine intake, suggesting that the full array of unmyelinated fibers associated with taste buds is not essential for the transmission of bitter taste. Capsaicin-treated animals showed a significant reduction in intake of normally highly preferred sodium chloride and sucrose concentrations. These results were probably not due to loss of peripheral unmyelinated afferent fibers per se, but rather to secondary central changes.

Effects of oral chemical irritation on taste.

Oral irritation was induced by rinses with capsicum oleoresin and with piperine, constituents of red and black pepper, respectively. The perceived intensities of two concentrations of each of four tastants representing the four classical taste qualities were evaluated after rinsing with these irritants. Comparing taste intensity after rinses with capsicum and after control rinses with emulsifying agents or water, there were significant decrements in taste intensity of citric acid and quinine, and on one concentration of sucrose, but no effect on salt. The effects of piperine were more broad, with significant decrements in perceived intensity relative to emulsion controls for all substances.

[Chemosensitive neuronal responses of the lateral hypothalamus in rats to simultaneous stimulation of the taste and viscero-chemoreceptors]. / Reaktsii khemosensitivnykh neironov lateral'nogo gipotalamusa krys pri odnovremennoi stimuliatsii vkusovykh i vistserokhemoretseptorov.

Adequate chemical stimulation of tongue receptors and viscerochemoreceptors was used for testing interactions between taste and viscerochemical information in units of the rat lateral hypothalamus. Some neurons only responded to the combined stimulation whereas other neurons responded to stimulation of one receptive zone only (taste or viscerochemical units).