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Chemical senses.

In the last decade, studies using approaches from molecular biology have substantially advanced our understanding of the early events in olfaction and taste. The many odorants that we can recognize may well interact with many distinct receptor proteins. Of the four taste qualities that we recognize, studies on salty and sour suggest that these tastes involve ion channels in the membrane of receptor cells while sweets and bitters bind to receptor proteins. Some volatiles (pheromones) play special roles in reproductive behavior via the vomeronasal organ (VNO) and the accessory olfactory system. Initial belief that humans lack a VNO has been questioned recently, thus raising the fascinating possibility of human pheromones. The roles that taste and smell play in the world of the newborn are very different. Acceptance of sweet and rejection of bitter appear to be hard-wired while the affect associated with odors depends much more on experience. Genetic variation may produce total losses (Kallman's syndrome produces anosmia and familial dysautonomia produces ageusia) or losses specific to certain stimuli. The best known of the specific anosmias is that for androstenone, which has no smell to some, a urinous smell to others, and a smell like sandalwood to still others. Analogous to the specific anosmias, some individuals are unable to taste PROP while others, supertasters, perceive PROP to be exceedingly bitter. Clinical studies reveal pathologies responsible for total or partial losses. The olfactory system, dependent on one cranial nerve, is more vulnerable than taste, and total anosmia is a relatively common clinical problem. Three cranial nerves carry taste and two of those nerves inhibit one another such that damage to one disinhibits the other and preserves over-all taste function. Total ageusia is very rare. Throughout these studies we see that taste and olfaction have different properties and often different functions (e.g. odor and reproduction). Yet taste and smell can also be integrated to determine what does or does not enter the body. In Adrian's words, "we are dealing with the sense organs which signal the quality of the air we breathe and that of the food and drink we propose to swallow."

Ageusia↗

Modulation of human cortical swallowing motor pathways after pleasant and aversive taste stimuli.

Human swallowing involves the integration of sensorimotor information with complexities such as taste; however, the interaction between the taste of food and its effects on swallowing control remains unknown. We assessed the effects of pleasant (sweet) and aversive (bitter) tastes on human cortical swallowing motor pathway excitability. Healthy adult male volunteers underwent a transcranial magnetic stimulation (TMS) mapping study (n = 9, mean age: 34 yr) to assess corticobulbar excitability before and up to 60 min after 10-min liquid infusions either 1) as swallowing tasks or 2) delivered directly into the stomach. Infusions were composed of sterile water (neutral), 10% glucose (sweet), and 0.5 mM quinine hydrochloride (bitter). The order of delivery was randomized, and each infusion was given on separate days. Pharyngeal motor-evoked potentials (PMEPs) were recorded from an intraluminal catheter as a measure of corticobulbar excitability and compared using repeated-measures and one-way ANOVA. After the swallowing task (water, glucose, or quinine), repeated-measures ANOVA revealed a significant time interaction across tastants (P </= 0.01). One-way ANOVA for each taste showed changes in PMEP amplitudes for both quinine (P </= 0.001) and glucose (P </= 0.009) solutions but not for water (P = 0.1). Subsequent t-tests showed that glucose and quinine reduced PMEPs by 47% (SD 34) and 37% (SD 54), respectively, at 30 min (P </= 0.03). No changes were observed after the infusion of any solution directly into the stomach (P = 0.51). In conclusion, cortical swallowing pathways are similarly modulated by both sweet and bitter tasting stimuli. Changes likely reflect a close interaction between taste and swallowing activity mediated in the central nervous system.

Adult↗

Dual actions of caffeine on voltage-dependent currents and intracellular calcium in taste receptor cells.

Although the numerous stimuli representing the taste quality of bitterness are known to be transduced through multiple mechanisms, recent studies have suggested an unpredicted complexity of the transduction pathways for individual bitter stimuli. To investigate this notion more thoroughly, a single prototypic bitter stimulus, caffeine, was studied by using patch-clamp and ratiometric imaging techniques on dissociated rat taste receptor cells. At behaviorally relevant concentrations, caffeine produced strong inhibition of outwardly and inwardly rectifying potassium currents. Caffeine additionally inhibited calcium current, produced a weaker inhibition of sodium current, and was without effect on chloride current. Consistent with its effects on voltage-dependent currents, caffeine caused a broadening of the action potential and an increase of the input resistance. Caffeine was an effective stimulus for elevation of intracellular calcium. This elevation was concentration dependent, independent of extracellular calcium or ryanodine, and dependent on intracellular stores as evidenced by thapsigargin treatment. These dual actions on voltage-activated ionic currents and intracellular calcium levels suggest that a single taste stimulus, caffeine, utilizes multiple transduction mechanisms.

Action Potentials↗

Differential effects of foods traditionally regarded as 'heating' and 'cooling' on prostaglandin E(2) production by a macrophage cell line.

Some components of natural foods may enhance or inhibit prostaglandin formation and potentially affect the inflammation condition. A macrophage cell line, RAW264.7, was employed to examine the effects of foods traditionally regarded as 'heating' or 'cooling' on the production of PGE(2), a well-known proinflammatory mediator. Foods traditionally regarded as 'heating' (litchi, longan, and dried longan) or 'cooling' (chrysanthemum flower, bitter gourd, and lotus seed plumule) were extracted sequentially with water and ethyl acetate. The water extracts (WE) and ethyl acetate extracts (EAE) were applied to RAW264.7 macrophages in the presence or absence of LPS (lipopolysaccharide). In the absence of LPS, the WEs from the 'heating foods', litchi, longan, or dried longan had a dose-dependent enhancing effect on PGE(2) production, with respective EC(50)s of 8.4, 16, and 11 mg/ml. This effect was accompanied by significant induction of COX-2 protein expression, as shown by Western blot analysis. In contrast, LPS-induced PGE(2) production was inhibited in a dose-dependent manner by the WEs of the 'cooling foods', chrysanthemum flower, bitter gourd, and lotus seed plumule, with respective IC(50)s of 0.6, 0.13, and 0.08 mg/ml. At the concentrations tested, none of the EAEs had any effect on basal PGE(2 )production, while LPS-induced PGE(2) production was inhibited or increased by the EAE from bitter gourd and longan, respectively. Water-soluble extracts of foods traditionally regarded as 'heating' enhanced basal PGE(2) production, while those from 'cooling' foods significantly inhibited LPS-induced PGE(2) production by the macrophage cell line. This subject merits further study to determine whether appropriate food selection may help patients suffering from chronic inflammatory conditions.

Animals↗

[Efficacy of tea blends in the treatment of dyspeptic disorders--an application observation].

BACKGROUND: Medicinal teas present one of the oldest galenic preparations of herbal remedies. Their use is primarily determined by tradition and empirics. One of their traditional domains are gastrointestinal disorders, which belong to the most frequent wellness disorders. While the effectiveness and compatibility of essential oils, modern drug extracts, and alcoholic extracts from bitters and etheric-oil drugs in the treatment of dyspeptic disorders have been documented in placebo-controlled clinical trials, little attention has so far been given to aqueous extracts from bitters and etheric-oil drugs, which are equivalent to the standard method of preparing herbal teas. PURPOSE: The presented application observation in clinical practice tried to give evidence for effectiveness and tolerability of medicinal teas in the treatment of dyspeptic disorders and to quantify their extent. MATERIAL AND METHODS: We collected information about effectiveness, compatibility, and side effects of herbal teas from 89 patients (w = 56; m = 33) suffering from dyspeptic disorders. The data were reported with a questionnaire that was sent to physicians and pharmacists experienced in phytotherapy. RESULTS: It could be shown that complaints in patients with primary dyspeptic symptoms (n = 79) decreased by an average of 74%. Final overall assessment revealed that the physicians as well as the patients estimated an effectiveness of 2.9 points as good (3 = good). Compatibility was considered as good to very good (4 = very good), with an average rating of 3.3 points. Two patients stopped therapy because of an extreme aversion to the bitter taste of the teas. No other serious side effects were reported. CONCLUSION: The herbal teas can be considered effective, very well tolerable and to a large extent free from serious side effects. However, due to the limited observation time, no final conclusion could be given concerning long-term compatibility.

Beverages↗

Nutritive value and haemolytic properties (in vitro) of the leaves of Vernonia amygdalina on human erythrocyte.

BACKGROUND: Vernonia amygdalina (Bitter leaf) is popularly consumed in many homes in Nigeria as a vegetable in soup preparation, while the infusion is used in folk medicine in the treatment of malaria fever. In this study, fresh leaves of Vernonia amygdalina were subjected to abrasion (to remove the bitter taste) as is normally done in soup preparation, subsequently the nutrient, anti-nutrient and zinc bioavailability of the processed and unprocessed leaf were determined. The heamolytic effect of the leaf infusion on human erythrocytes (Genotype-SS, AS, AA) was also determined. RESULT: The study revealed that Vernonia amygdalina leaf has high protein (33.3%), fat (10.1%), crude fibre (29.2%), ash (11.7%), mineral (Na, K, Ca, Mg, Zn & Fe), phytate (1015.4mg/100g) and tannin (0.6%) content, while it contain low cyanide (1.1mg/kg). Abrasion of the leaf caused a significant decrease (P<0.05) in both the nutrient and antinutrient content of the leaf except in carbohydrate where there was a significant increase (P<0.05) and Mg where there was no significant change (P>0.05). The result of the calculated [Ca][phytate]/ [Zn] molar ratio (the best index for the prediction of Zn bioavailability) indicated that the phytate content of both the processed and unprocessed Vernonia amygdalina leaf will not reduce the Zn content to a critical level (0.5mol./kg). Further studies on the leaf revealed that the infusion induced the haemolysis of human erythrocyte (In vitro). Human genotype-SS (1024) were highly susceptible to haemolysis induced by Vernonia amygdalina infusion, genotype-AS moderately susceptible (512) while genotype-AA (256) is highly resistant to haemolysis induced by the same infusion. CONCLUSION: Bitter leaf has high nutrient and antinutrient content, however, abrasion will bring about a significant decrease (P<0.05) in both. The infusion of the Vernonia amygdalina leaf induces the haemolysis of mammalian erythrocyte in vitro, with Human-SS having the highest susceptibility.

Biological Availability↗

Comparison of the responses of the chorda tympani and glossopharyngeal nerves to taste stimuli in C57BL/6J mice.

BACKGROUND: Recent progress in discernment of molecular pathways of taste transduction underscores the need for comprehensive phenotypic information for the understanding of the influence of genetic factors in taste. To obtain information that can be used as a base line for assessment of effects of genetic manipulations in mice taste, we have recorded the whole-nerve integrated responses to a wide array of taste stimuli in the chorda tympani (CT) and glossopharyngeal (NG) nerves, the two major taste nerves from the tongue. RESULTS: In C57BL/6J mice the responses in the two nerves were not the same. In general sweeteners gave larger responses in the CT than in the NG, while responses to bitter taste in the NG were larger. Thus the CT responses to cyanosuosan, fructose, NC00174, D-phenylalanline and sucrose at all concentrations were significantly larger than in the NG, whereas for acesulfame-K, L-proline, saccharin and SC45647 the differences were not significant. Among bitter compounds amiloride, atropine, cycloheximide, denatonium benzoate, L-phenylalanine, 6-n-propyl-2-thiouracil (PROP) and tetraethyl ammonium chloride (TEA) gave larger responses in the NG, while the responses to brucine, chloroquine, quinacrine, quinine hydrochloride (QHCl), sparteine and strychnine, known to be very bitter to humans, were not significantly larger in the NG than in the CT. CONCLUSION: These data provide a comprehensive survey and comparison of the taste sensitivity of the normal C57BL/6J mouse against which the effects of manipulations of its gustatory system can be better assessed.

Acids↗

Effects of caloric deprivation and satiety on sensitivity of the gustatory system.

BACKGROUND: Sensitivity of the gustatory system could be modulated by a number of short-term and long-term factors such as body mass, gender, age, local and systemic diseases and pathological processes, excessive alcohol drinking, drug dependence, smoking, composition of oral fluid, state of oral hygiene, consumption of some foods among many others. A few studies have demonstrated the effects of hunger and caloric satiety on sensitivity of the gustatory system in obese humans and animals. The aim of the present study was to assess the effects of short-term caloric deprivation and satiety on recognition taste thresholds of healthy, non-smoking, non-drinking, non-obese young male subjects. The two-alternative forced-choice technique was used to measure taste threshold. RESULTS: Recognition thresholds for sucrose and salt were significantly lower during fasting state than after a meal (t = 2.23, P < 0.05, and t = 2.86, P < 0.02, respectively) while the values of recognition thresholds for bitter substances in fasting state and after caloric loading did not differ significantly. CONCLUSIONS: Short-term caloric deprivation in our study model was associated with increased taste sensitivity to sweet and salty substances compared to satiated state while taste sensitivity to bitter substances was not affected by the conditions of measurements. Selective modulation of sensitivity of the gustatory system might reflect the different biological importance of salty, sweet and bitter qualities of taste.

Adult↗

The human sweet tooth.

Humans love the taste of sugar and the word "sweet" is used to describe not only this basic taste quality but also something that is desirable or pleasurable, e.g., la dolce vita. Although sugar or sweetened foods are generally among the most preferred choices, not everyone likes sugar, especially at high concentrations. The focus of my group's research is to understand why some people have a sweet tooth and others do not. We have used genetic and molecular techniques in humans, rats, mice, cats and primates to understand the origins of sweet taste perception. Our studies demonstrate that there are two sweet receptor genes (TAS1R2 and TAS1R3), and alleles of one of the two genes predict the avidity with which some mammals drink sweet solutions. We also find a relationship between sweet and bitter perception. Children who are genetically more sensitive to bitter compounds report that very sweet solutions are more pleasant and they prefer sweet carbonated beverages more than milk, relative to less bitter-sensitive peers. Overall, people differ in their ability to perceive the basic tastes, and particular constellations of genes and experience may drive some people, but not others, toward a caries-inducing sweet diet. Future studies will be designed to understand how a genetic preference for sweet food and drink might contribute to the development of dental caries.

Journal Article↗

Mouse taste cells with G protein-coupled taste receptors lack voltage-gated calcium channels and SNAP-25.

BACKGROUND: Taste receptor cells are responsible for transducing chemical stimuli from the environment and relaying information to the nervous system. Bitter, sweet and umami stimuli utilize G-protein coupled receptors which activate the phospholipase C (PLC) signaling pathway in Type II taste cells. However, it is not known how these cells communicate with the nervous system. Previous studies have shown that the subset of taste cells that expresses the T2R bitter receptors lack voltage-gated Ca2+ channels, which are normally required for synaptic transmission at conventional synapses. Here we use two lines of transgenic mice expressing green fluorescent protein (GFP) from two taste-specific promoters to examine Ca2+ signaling in subsets of Type II cells: T1R3-GFP mice were used to identify sweet- and umami-sensitive taste cells, while TRPM5-GFP mice were used to identify all cells that utilize the PLC signaling pathway for transduction. Voltage-gated Ca2+ currents were assessed with Ca2+ imaging and whole cell recording, while immunocytochemistry was used to detect expression of SNAP-25, a presynaptic SNARE protein that is associated with conventional synapses in taste cells. RESULTS: Depolarization with high K+ resulted in an increase in intracellular Ca2+ in a small subset of non-GFP labeled cells of both transgenic mouse lines. In contrast, no depolarization-evoked Ca2+ responses were observed in GFP-expressing taste cells of either genotype, but GFP-labeled cells responded to the PLC activator m-3M3FBS, suggesting that these cells were viable. Whole cell recording indicated that the GFP-labeled cells of both genotypes had small voltage-dependent Na+ and K+ currents, but no evidence of Ca2+ currents. A subset of non-GFP labeled taste cells exhibited large voltage-dependent Na+ and K+ currents and a high threshold voltage-gated Ca2+ current. Immunocytochemistry indicated that SNAP-25 was expressed in a separate population of taste cells from those expressing T1R3 or TRPM5. These data indicate that G protein-coupled taste receptors and conventional synaptic signaling mechanisms are expressed in separate populations of taste cells. CONCLUSION: The taste receptor cells responsible for the transduction of bitter, sweet, and umami stimuli are unlikely to communicate with nerve fibers by using conventional chemical synapses.

Animals↗

Diet-induced plasticity in the taste system of an insect: localization to a single transduction pathway in an identified taste cell.

We studied exposure-induced sensitivity changes in an identified taste cell from Manduca sexta, a herbivorous caterpillar. This taste cell occurs within the lateral styloconic sensillum and responds selectively to compounds that humans characterize as bitter (e.g. caffeine, salicin and aristolochic acid). We made extracellular recordings from several classes of identified taste cell within the lateral sensillum, both before and after dietary exposure (for 48 h) to a suprathreshold concentration of caffeine, salicin or aristolochic acid. Our results revealed (1) that dietary exposure to caffeine desensitized the bitter-sensitive taste cell to caffeine, whereas dietary exposure to salicin or aristolochic acid did not desensitize the same taste cell to salicin or to aristolochic acid; (2) that dietary exposure to caffeine failed to alter the responsiveness of the sugar-, salt- or inositol-sensitive taste cells within the same sensillum; (3) that the caffeine-induced desensitization phenomenon generalized to salicin, a compound that stimulates the same transduction pathway as caffeine, but not to aristolochic acid, a compound that stimulates a different pathway; and (4) that chronically stimulating the lateral sensillum with caffeine, in the absence of ingestion, was sufficient to induce desensitization. We conclude that caffeine causes desensitization through a direct effect on a single transduction pathway within the bitter-sensitive taste cell.

Animals↗

Selective adaptation to noxious foods by a herbivorous insect.

When animals repeatedly sample a noxious food over a period of 1-4 days, they can markedly reduce their aversive behavioral response to the diet's unpleasant taste (e.g. 'bitterness') or toxic effects. This long-term adaptation process is selective, however, permitting insects to adapt physiologically to some but not all noxious foods. We hypothesized (i) that the selective nature of this adaptation process stems from the fact that some unpalatable foods are toxic while others are harmless and (ii) that insects have more difficulty adapting to foods that are both unpalatable and toxic. Our model system consisted of Manduca sexta caterpillars and two compounds that taste bitter to humans and elicit an aversive behavioral response in this insect (salicin and aristolochic acid). We found that 2 days of exposure to a salicin diet completely adapted the aversive response of the caterpillars to salicin, but that exposure to an aristolochic acid diet failed to adapt the aversive response to aristolochic acid. We determined that M. sexta could not adapt to the aristolochic acid diet because it lacked mechanisms for reducing the compound's toxicity. In contrast, the salicin diet did not produce any apparent toxic effects, and the caterpillars adapted to its aversive taste within 12 h of exposure. We also found that the salicin adaptation phenomenon (i) was mediated by the central gustatory system, (ii) generalized to salicin concentrations that were twice those in the adapting diet and (iii) offset spontaneously when the caterpillar was transferred to a salicin-free diet. We propose that toxicity is a more significant barrier to dietary adaptation than 'bitterness' in this insect.

Adaptation, Physiological↗

Quantitative taste evaluation of total enteral nutrients.

The purpose of this study was to evaluate quantitatively the taste of the various total enteral nutrients marketed in Japan using human gustatory sensation tests and an artificial taste sensor. In the human gustatory sensation test, four basic taste intensities (sweetness, saltiness, sourness, and bitterness), as well as 15 kinds of palatability scales, were evaluated according to the semantic differential (SD) method. Among 15 palatability items, the item; difficult to drink/easy to drink, was adopted as an overall palatability since it shows the highest factor loading by factor analysis. The overall palatability was found to be highly positively correlated with sweetness and sourness, but negatively correlated with bitterness and saltiness. Addition of a flavour to the amino acid-based enteral nutrient AminolebanEN significantly improved its palatability. This effect is presumably due to sour components of the flavour, such as citric acid, which reduce the bitterness intensity of branched-chain amino acids in the product. The sweetness and sourness intensities predicted by the taste sensor showed a high correlation with the results obtained in the human gustatory sensation tests. The taste sensor was able to predict the overall palatability of the total enteral nutrients with high accuracy. The products could be classified into three groups (peptide-based, amino-acid-based, and protein-based) by principal component analysis using sensor output of 8 channels. The products could be also classified into four groups; peptide-based, amino-acid-based, and protein-based and flavor addition group by principal component analysis using sensor output of channels 1, 3, 4 and 7, which are specific to basic tastes. The taste sensor could therefore be useful in predicting the taste or palatability of total enteral nutrients, and could contribute to attempts to improve compliance for such products and for enteral nutrients.

Biosensing Techniques↗

[Preparing oral dosage form of ketamine in the hospital for simplicity and patient compliance--preparations using agar].

Ketamine has been widely used in the operation as intravenous and intramuscular injections, since ketamine has dissociative anesthetic properties. When it is given in sub-anesthetic dose, ketamine is known to have an analgesic effect. The analgesic effect is observed for patients with neuropathic pain when administrated not only by injection but also orally. In Japan, since ketamine is not commercially available except injection forms, patients have to take it as solution of injections for the oral medication. Since the solution of injections has extremely bitter taste, patients intensely desire the development of preparations without the bitterness. In the present study, we prepared oral gel dosage forms of ketamine using agar. It is simple to prepare this dosage form, and most pharmacists can prepare it easily in many hospitals. This gel dosage form met content uniformity requirements and the shape of that was maintained intact during the dissolution test (for 10 hours). The release rate was reduced by additions of additives such as sugar and a flavor in the gel. The reason for the reduction in release could be the suppression of ketamine diffusion depended on the micro-viscosity of solution in the gel. The ketamine contents and the release profile of the gel preparations were unchanged at the room temperature for 12-week storage. The gel preparations in this study would be useful for the oral medication of ketamine, since it is easy for patients to carry them when they go out and the intensely bitter taste could be improved by the addition of a flavor.

Administration, Oral↗

Mouse taste buds use serotonin as a neurotransmitter.

Synapses between gustatory receptor cells and primary sensory afferent fibers transmit the output signal from taste buds to the CNS. Several transmitter candidates have been proposed for these synapses, including serotonin (5-HT), glutamate, acetylcholine, ATP, peptides, and others, but, to date, none has been unambiguously identified. We used Chinese hamster ovary cells stably expressing 5-HT2C receptors as biodetectors to monitor 5-HT release from taste buds. When taste buds were depolarized with KCl or stimulated with bitter, sweet, or sour (acid) tastants, serotonin was released. KCl- and acid-induced 5-HT release, but not release attributable to sweet or bitter stimulation, required Ca2+ influx. In contrast, 5-HT release evoked by sweet and bitter stimulation seemed to be triggered by intracellular Ca2+ release. These experiments strongly implicate serotonin as a taste bud neurotransmitter and reveal unexpected transmitter release mechanisms.

Adenosine Triphosphate↗

Analysis of swertiamarin in Swertia herb and preparations containing this crude drug by capillary electrophoresis.

Swertia herb (florescent whole plantof Swertia japonica, Gentianaceae) has long been utilized as a folk medicine in Japan. It is often blended in general gastroenteric drugs as a bitter stomachic. Swertiamarin, a bitter secoiridoid glycoside, is the representative constituent of this crude drug and Swertia herb is normally evaluated by the swertiamarin content. To date, papers have described the discrimination of Swertia herbs from other bitter crude drugs, estimation of swertiamarin and seasonal variation in swertiamarin content using thin-layer chromatography, while other papers have reported quantitative determination of swertiamarin using high-performance liquid chromatography (HPLC). In our previous papers, we reported analyses of the constituents of some crude drugs using capillary electrophoresis (CE). To aid in the evaluation of crude drugs, we succeeded in our attempt to separate and determine the quantity of swertiamarin in Swertia herb. Subsequently, we applied the same analytical condition to estimate the swertiamarin contents in Japanese pharmacopoeia stomachic preparations, in OTC gastroenteric drugs and in OTC hair tonics containing Swertia herb.

Chromatography, High Pressure Liquid↗

Quality-specific effects of aging on the human taste system.

Elderly persons are known to have elevated taste thresholds, with those for bitter more affected by age, for example, than those for sweet. Do analogous quality-specific effects occur at suprathreshold levels? Young (mean age = 20.3 years, SD = 2.99) and elderly (mean age = 72.5 years, SD = 4.58) subjects made magnitude estimates of sweetness, bitterness, sourness, and saltiness for the unmixed components sucrose, caffeine, citric acid, and NaCl at three concentration levels for each. They also made magnitude estimates of the separate taste qualities in two-component mixtures of sucrose with each of the other three qualities, at various levels of the two components in each mixture. Magnitude estimates of taste intensity were interweaved with magnitude estimates of the heaviness of six weights, which subjects were to judge on the same subjective intensity scale: This is the calibration feature of the method of magnitude matching, and permits the comparison of elderly and young subjects on the absolute intensity of tastes. When unmixed components were judged, elderly subjects found the characteristic tastes of caffeine and citric acid less intense than, but those of sucrose and NaCl as intense as, younger subjects did. In judging mixtures, the elderly found bitterness, but not the other three qualities, less intense than did the young subjects.

Adult↗

The riddle of L-glucose pentaacetate insulinotropic action (review).

The two anomers of L-glucose pentaacetate were recently found to stimulate insulin release. The insulinotropic action of these esters cannot be attributed to the catabolism in islet cells of their glucidic or acetic moieties. The present review deals with an alternative hypothesis. It is proposed that L-glucose pentaacetate itself directly interacts with a yet unidentified receptor leading to plasma membrane depolarization, induction of electrical activity and increase in the cytosolic concentration of ionized Ca2+. This process displays analogies with the identification of bitter compounds by taste buds. Thus, beta-L-glucose pentaacetate indeed displays a bitter, but no sweet, taste. Purified islet B-cells contain the alpha-gustducin G-protein involved in the perception of bitter taste by taste buds. The pentaacetate ester of beta-L-glucose decreases 86Rb outflow from prelabelled islets, provokes bioelectrical activity in islet B-cells and may induce oscillations of cytosolic Ca2+ in these insulin-producing cells. The effects of beta-L-glucose pentaacetate upon glucagon and somatostatin secretion by the isolated perfused pancreas are also compatible with the present hypothesis. It is proposed that the L-glucose pentaacetate anomers could be used as novel insulinotropic tools in the treatment of non-insulin-dependent diabetes mellitus.

Animals↗