25 results on '"Dotson CD"'
Search Results
2. Y1 receptors modulate taste-related behavioral responsiveness in male mice to prototypical gustatory stimuli.
- Author
-
Malone IG, Hunter BK, Rossow HL, Herzog H, Zolotukhin S, Munger SD, and Dotson CD
- Subjects
- Animals, Male, Mammals metabolism, Mice, Mice, Knockout, Neuropeptide Y genetics, Neuropeptide Y metabolism, Peptide YY metabolism, Receptors, Neuropeptide Y genetics, Receptors, Neuropeptide Y metabolism, Taste, Taste Buds metabolism
- Abstract
Mammalian taste bud cells express receptors for numerous peptides implicated elsewhere in the body in the regulation of metabolism, nutrient assimilation, and satiety. The perturbation of several peptide signaling pathways in the gustatory periphery results in changes in behavioral and/or physiological responsiveness to subsets of taste stimuli. We previously showed that Peptide YY (PYY) - which is present in both saliva and in subsets of taste cells - can affect behavioral taste responsiveness and reduce food intake and body weight. Here, we investigated the contributions of taste bud-localized receptors for PYY and the related Neuropeptide Y (NPY) on behavioral taste responsiveness. Y1R, but not Y2R, null mice show reduced responsiveness to sweet, bitter, and salty taste stimuli in brief-access taste tests; similar results were seen when wildtype mice were exposed to Y receptor antagonists in the taste stimuli. Finally, mice in which the gene encoding the NPY propeptide was deleted also showed reduced taste responsiveness to sweet and bitter taste stimuli. Collectively, these results suggest that Y1R signaling, likely through its interactions with NPY, can modulate peripheral taste responsiveness in mice., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
3. Taste Receptor Cells in Mice Express Receptors for the Hormone Adiponectin.
- Author
-
Crosson SM, Marques A, Dib P, Dotson CD, Munger SD, and Zolotukhin S
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Mice, Knockout, Taste Buds metabolism, Adiponectin metabolism, Receptors, Adiponectin biosynthesis, Taste Buds cytology
- Abstract
The metabolic hormone adiponectin is secreted into the circulation by adipocytes and mediates key biological functions, including insulin sensitivity, adipocyte development, and fatty acid oxidation. Adiponectin is also abundant in saliva, where its functions are poorly understood. Here we report that murine taste receptor cells (TRCs) express specific adiponectin receptors and may be a target for salivary adiponectin. This is supported by the presence of all three known adiponectin receptors in transcriptomic data obtained by RNA-seq analysis of purified circumvallate (CV) taste buds. As well, immunohistochemical analysis of murine CV papillae showed that two adiponectin receptors, ADIPOR1 and T-cadherin, are localized to subsets of TRCs. Immunofluorescence for T-cadherin was primarily co-localized with the Type 2 TRC marker phospholipase C β2, suggesting that adiponectin signaling could impact sweet, bitter, or umami taste signaling. However, adiponectin null mice showed no differences in behavioral lick responsiveness compared with wild-type controls in brief-access lick testing. AAV-mediated overexpression of adiponectin in the salivary glands of adiponectin null mice did result in a small but significant increase in behavioral lick responsiveness to the fat emulsion Intralipid. Together, these results suggest that salivary adiponectin can affect TRC function, although its impact on taste responsiveness and peripheral taste coding remains unclear., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2019
- Full Text
- View/download PDF
4. Exploring Ethnic Differences in Taste Perception.
- Author
-
Williams JA, Bartoshuk LM, Fillingim RB, and Dotson CD
- Subjects
- Adolescent, Adult, Black or African American, Analysis of Variance, Citric Acid pharmacology, Female, Hispanic or Latino, Humans, Male, Middle Aged, Quinine pharmacology, Sodium Chloride pharmacology, Sucrose pharmacology, Taste Perception drug effects, White People, Young Adult, Taste Perception physiology
- Abstract
It is well known that nutritional intake can vary substantially as a function of demographic variables such as ethnicity and/or sex. Although a variety of factors are known to underlie the relationship between these demographic variables and nutritional intake, it is interesting to speculate that variation in food intake associated with ethnicity or sex may result, in part, from differences in the perceived taste of foods in these different populations. Thus, we initiated a study to evaluate taste responsiveness in different ethnic groups. Moreover, because of the known differences in taste responsiveness between males and females, analyses were stratified by sex. The ethnic groups tested differed significantly from one another in reported perceived taste intensity. Our results showed that Hispanics and African Americans rated taste sensations higher than non-Hispanic Whites and that these differences were more pronounced in males. Understanding the nature of these differences in taste perception is important, because taste perception may contribute to dietary health risk. When attempting to modify diet, individuals of different ethnicities may require personalized interventions that take into account the different sensory experience that these individuals may have when consuming foods., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2016
- Full Text
- View/download PDF
5. Using Animal Models to Determine the Role of Gustatory Neural Input in the Control of Ingestive Behavior and the Maintenance of Body Weight.
- Author
-
Ciullo DL and Dotson CD
- Abstract
Introduction: Decades of research have suggested that nutritional intake contributes to the development of human disease, mainly by influencing the development of obesity and obesity-related conditions. A relatively large body of research indicates that functional variation in human taste perception can influence nutritional intake as well as body mass accumulation. However, there are a considerable number of studies that suggest that no link between these variables actually exists. These discrepancies in the literature likely result from the confounding influence of a variety of other, uncontrolled, factors that can influence ingestive behavior., Strategy: In this review, the use of controlled animal experimentation to alleviate at least some of these issues related to the lack of control of experimental variables is discussed. Specific examples of the use of some of these techniques are examined., Discussion and Conclusions: The review will close with some specific suggestions aimed at strengthening the link between gustatory neural input and its putative influence on ingestive behaviors and the maintenance of body weight.
- Published
- 2015
- Full Text
- View/download PDF
6. TAS2R bitter taste receptors regulate thyroid function.
- Author
-
Clark AA, Dotson CD, Elson AE, Voigt A, Boehm U, Meyerhof W, Steinle NI, and Munger SD
- Subjects
- Adult, Animals, Calcium metabolism, Cell Line, Female, Gene Expression, Humans, Immunohistochemistry, Ligands, Male, Mice, Mice, Transgenic, Middle Aged, Polymorphism, Single Nucleotide, Receptors, G-Protein-Coupled agonists, Receptors, G-Protein-Coupled genetics, Thyroid Gland cytology, Thyroid Hormones metabolism, Thyrotropin metabolism, Tissue Distribution, Receptors, G-Protein-Coupled metabolism, Thyroid Gland metabolism
- Abstract
Dysregulation of thyroid hormones triiodothyronine and thyroxine (T3/T4) can impact metabolism, body composition, and development. Thus, it is critical to identify novel mechanisms that impact T3/T4 production. We found that type 2 taste receptors (TAS2Rs), which are activated by bitter-tasting compounds such as those found in many foods and pharmaceuticals, negatively regulate thyroid-stimulating hormone (TSH)-dependent Ca(2+) increases and TSH-dependent iodide efflux in thyrocytes. Immunohistochemical Tas2r-dependent reporter expression and real-time PCR analyses reveal that human and mouse thyrocytes and the Nthy-Ori 3-1 human thyrocyte line express several TAS2Rs. Five different agonists for thyrocyte-expressed TAS2Rs reduced TSH-dependent Ca(2+) release in Nthy-Ori 3-1 cells, but not basal Ca(2+) levels, in a dose-dependent manner. Ca(2+) responses were unaffected by 6-n-propylthiouracil, consistent with the expression of an unresponsive variant of its cognate receptor, TAS2R38, in these cells. TAS2R agonists also inhibited basal and TSH-dependent iodide efflux. Furthermore, a common TAS2R42 polymorphism is associated with increased serum T4 levels in a human cohort. Our findings indicate that TAS2Rs couple the detection of bitter-tasting compounds to changes in thyrocyte function and T3/T4 production. Thus, TAS2Rs may mediate a protective response to overingestion of toxic materials and could serve as new druggable targets for therapeutic treatment of hypo- or hyperthyroidism., (© FASEB.)
- Published
- 2015
- Full Text
- View/download PDF
7. Modulation of taste responsiveness by the satiation hormone peptide YY.
- Author
-
La Sala MS, Hurtado MD, Brown AR, Bohórquez DV, Liddle RA, Herzog H, Zolotukhin S, and Dotson CD
- Subjects
- Animals, Eating, Mice, Mice, Knockout, Peptide YY genetics, Receptors, Neuropeptide Y genetics, Receptors, Neuropeptide Y metabolism, Taste Buds metabolism, Peptide YY metabolism, Satiety Response, Taste
- Abstract
It has been hypothesized that the peripheral taste system may be modulated in the context of an animal's metabolic state. One purported mechanism for this phenomenon is that circulating gastrointestinal peptides modulate the functioning of the peripheral gustatory system. Recent evidence suggests endocrine signaling in the oral cavity can influence food intake (FI) and satiety. We hypothesized that these hormones may be affecting FI by influencing taste perception. We used immunohistochemistry along with genetic knockout models and the specific reconstitution of peptide YY (PYY) in saliva using gene therapy protocols to identify a role for PYY signaling in taste. We show that PYY is expressed in subsets of taste cells in murine taste buds. We also show, using brief-access testing with PYY knockouts, that PYY signaling modulates responsiveness to bitter-tasting stimuli, as well as to lipid emulsions. We show that salivary PYY augmentation, via viral vector therapy, rescues behavioral responsiveness to a lipid emulsion but not to bitter stimuli and that this response is likely mediated via activation of Y2 receptors localized apically in taste cells. Our findings suggest distinct functions for PYY produced locally in taste cells vs. that circulating systemically.
- Published
- 2013
- Full Text
- View/download PDF
8. Salivary peptide tyrosine-tyrosine 3-36 modulates ingestive behavior without inducing taste aversion.
- Author
-
Hurtado MD, Sergeyev VG, Acosta A, Spegele M, La Sala M, Waler NJ, Chiriboga-Hurtado J, Currlin SW, Herzog H, Dotson CD, Gorbatyuk OS, and Zolotukhin S
- Subjects
- Aminophylline, Animals, Conditioning, Psychological drug effects, Eating drug effects, Extracellular Signal-Regulated MAP Kinases metabolism, Gene Expression Regulation drug effects, Gene Expression Regulation genetics, Glucagon-Like Peptide 1 metabolism, Humans, Iodine Isotopes pharmacokinetics, Male, Mice, Mice, Inbred C57BL, Oxytocin metabolism, Peptide YY chemistry, Proto-Oncogene Proteins c-fos metabolism, Satiation drug effects, Tyrosine 3-Monooxygenase metabolism, Vasopressins metabolism, alpha-MSH metabolism, Feeding Behavior drug effects, Peptide Fragments pharmacology, Peptide YY deficiency, Saliva enzymology
- Abstract
Hormone peptide tyrosine-tyrosine (PYY) is secreted into circulation from the gut L-endocrine cells in response to food intake, thus inducing satiation during interaction with its preferred receptor, Y2R. Clinical applications of systemically administered PYY for the purpose of reducing body weight were compromised as a result of the common side effect of visceral sickness. We describe here a novel approach of elevating PYY in saliva in mice, which, although reliably inducing strong anorexic responses, does not cause aversive reactions. The augmentation of salivary PYY activated forebrain areas known to mediate feeding, hunger, and satiation while minimally affecting brainstem chemoreceptor zones triggering nausea. By comparing neuronal pathways activated by systemic versus salivary PYY, we identified a metabolic circuit associated with Y2R-positive cells in the oral cavity and extending through brainstem nuclei into hypothalamic satiety centers. The discovery of this alternative circuit that regulates ingestive behavior without inducing taste aversion may open the possibility of a therapeutic application of PYY for the treatment of obesity via direct oral application.
- Published
- 2013
- Full Text
- View/download PDF
9. Peptide regulators of peripheral taste function.
- Author
-
Dotson CD, Geraedts MC, and Munger SD
- Subjects
- Animals, Humans, Signal Transduction, Taste Buds metabolism, Peptides metabolism, Taste
- Abstract
The peripheral sensory organ of the gustatory system, the taste bud, contains a heterogeneous collection of sensory cells. These taste cells can differ in the stimuli to which they respond and the receptors and other signaling molecules they employ to transduce and encode those stimuli. This molecular diversity extends to the expression of a varied repertoire of bioactive peptides that appear to play important functional roles in signaling taste information between the taste cells and afferent sensory nerves and/or in processing sensory signals within the taste bud itself. Here, we review studies that examine the expression of bioactive peptides in the taste bud and the impact of those peptides on taste functions. Many of these peptides produced in taste buds are known to affect appetite, satiety or metabolism through their actions in the brain, pancreas and other organs, suggesting a functional link between the gustatory system and the neural and endocrine systems that regulate feeding and nutrient utilization., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
10. Variation in the gene TAS2R13 is associated with differences in alcohol consumption in patients with head and neck cancer.
- Author
-
Dotson CD, Wallace MR, Bartoshuk LM, and Logan HL
- Subjects
- Female, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide genetics, Sequence Analysis, DNA, Taste Threshold genetics, Alcohol Drinking genetics, Genetic Variation genetics, Head and Neck Neoplasms genetics, Receptors, G-Protein-Coupled genetics
- Abstract
Variation in responsiveness to bitter-tasting compounds has been associated with differences in alcohol consumption. One strong genetic determinant of variation in bitter taste sensitivity is alleles of the TAS2R gene family, which encode chemosensory receptors sensitive to a diverse array of natural and synthetic compounds. Members of the TAS2R family, when expressed in the gustatory system, function as bitter taste receptors. To better understand the relationship between TAS2R function and alcohol consumption, we asked if TAS2R variants are associated with measures of alcohol consumption in a head and neck cancer patient cohort. Factors associated with increased alcohol intake are of strong interest to those concerned with decreasing the incidence of cancers of oral and pharyngeal structures. We found a single nucleotide polymorphism (SNP) located within the TAS2R13 gene (rs1015443 [C1040T, Ser259Asn]), which showed a significant association with measures of alcohol consumption assessed via the Alcohol Use Disorders Identification Test (AUDIT). Analyses with other SNPs in close proximity to rs1015443 suggest that this locus is principally responsible for the association. Thus, our results provide additional support to the emerging hypothesis that genetic variation in bitter taste receptors can impact upon alcohol consumption.
- Published
- 2012
- Full Text
- View/download PDF
11. The consequences of gustatory deafferentation on body mass and feeding patterns in the rat.
- Author
-
Dotson CD, Colbert CL, Garcea M, Smith JC, and Spector AC
- Subjects
- Animal Feed analysis, Animals, Appetite physiology, Corn Oil chemistry, Diet, Dietary Fats, Unsaturated analysis, Drinking Behavior physiology, Energy Intake physiology, Male, Milk chemistry, Rats, Rats, Sprague-Dawley, Stomach physiology, Sucrose chemistry, Sucrose pharmacology, Sweetening Agents chemistry, Afferent Pathways physiology, Body Weight physiology, Denervation, Feeding Behavior physiology, Stomach innervation
- Abstract
The contribution of orosensory signals, especially taste, on body mass, and feeding and drinking patterns in the rat was examined. Gustatory deafferentation was produced by bilateral transection of the chorda tympani, glossopharyngeal, and greater superficial petrosal nerves. Total calories consumed from sweetened-milk diet and oil-chow mash by the nerve-transected rats significantly decreased relative to sham-operated controls, mostly attributable to decreases in bout number, but not size. Nevertheless, caloric intake steadily increased over the postsurgical observation period, but body mass remained below both presurgical baseline and control levels and did not significantly increase over this time. After the sweetened-milk diet/oil-chow mash phase, rats received a series of sucrose preference tests. Interestingly, the nerve-transected rats preferred sucrose, and intake did not differ from controls, likely due to the stimulus sharing some nontaste chemosensory properties with the sweetened-milk diet. The neurotomized rats initiated a greater number of sucrose-licking bouts that were smaller in size and slower in licking rate, compared with control rats, and, unlike in control rats, the latter two bout parameters did not vary across concentration. Thus, in the absence of gustatory neural input, body mass is more stable compared with the progressive trajectory of weight gain seen in intact rats, and caloric intake initially decreases but recovers. The consequences of gustatory neurotomy on processes that determine meal initiation (bout number) and meal termination (bout size) are not fixed and appear to be influenced by presurgical experience with food stimuli coupled with its nongustatory chemosensory properties.
- Published
- 2012
- Full Text
- View/download PDF
12. Transformation of postingestive glucose responses after deletion of sweet taste receptor subunits or gastric bypass surgery.
- Author
-
Geraedts MC, Takahashi T, Vigues S, Markwardt ML, Nkobena A, Cockerham RE, Hajnal A, Dotson CD, Rizzo MA, and Munger SD
- Subjects
- Animals, Cells, Cultured, Feces chemistry, Fructose pharmacology, Glucagon-Like Peptide 1 pharmacology, Glucose pharmacology, Glucose Tolerance Test, Glyburide pharmacology, Homeostasis drug effects, Homeostasis physiology, Hypoglycemic Agents pharmacology, Ileum drug effects, Ileum metabolism, Insulin metabolism, Insulin Secretion, Intestine, Large drug effects, Intestine, Large metabolism, Islets of Langerhans drug effects, Islets of Langerhans metabolism, KATP Channels metabolism, Mice, Rats, Sucrose analogs & derivatives, Sucrose pharmacology, Taste Buds drug effects, Gastric Bypass, Glucagon-Like Peptide 1 metabolism, Glucose metabolism, Receptors, G-Protein-Coupled metabolism, Taste Buds metabolism
- Abstract
The glucose-dependent secretion of the insulinotropic hormone glucagon-like peptide-1 (GLP-1) is a critical step in the regulation of glucose homeostasis. Two molecular mechanisms have separately been suggested as the primary mediator of intestinal glucose-stimulated GLP-1 secretion (GSGS): one is a metabotropic mechanism requiring the sweet taste receptor type 2 (T1R2) + type 3 (T1R3) while the second is a metabolic mechanism requiring ATP-sensitive K(+) (K(ATP)) channels. By quantifying sugar-stimulated hormone secretion in receptor knockout mice and in rats receiving Roux-en-Y gastric bypass (RYGB), we found that both of these mechanisms contribute to GSGS; however, the mechanisms exhibit different selectivity, regulation, and localization. T1R3(-/-) mice showed impaired glucose and insulin homeostasis during an oral glucose challenge as well as slowed insulin granule exocytosis from isolated pancreatic islets. Glucose, fructose, and sucralose evoked GLP-1 secretion from T1R3(+/+), but not T1R3(-/-), ileum explants; this secretion was not mimicked by the K(ATP) channel blocker glibenclamide. T1R2(-/-) mice showed normal glycemic control and partial small intestine GSGS, suggesting that T1R3 can mediate GSGS without T1R2. Robust GSGS that was K(ATP) channel-dependent and glucose-specific emerged in the large intestine of T1R3(-/-) mice and RYGB rats in association with elevated fecal carbohydrate throughout the distal gut. Our results demonstrate that the small and large intestines utilize distinct mechanisms for GSGS and suggest novel large intestine targets that could mimic the improved glycemic control seen after RYGB.
- Published
- 2012
- Full Text
- View/download PDF
13. Distribution of Y-receptors in murine lingual epithelia.
- Author
-
Hurtado MD, Acosta A, Riveros PP, Baum BJ, Ukhanov K, Brown AR, Dotson CD, Herzog H, and Zolotukhin S
- Subjects
- Animals, Cell Line, Humans, In Situ Hybridization, In Vitro Techniques, Mice, Receptors, Neuropeptide Y genetics, Reverse Transcriptase Polymerase Chain Reaction, Epithelium metabolism, Receptors, Neuropeptide Y metabolism, Tongue cytology
- Abstract
Peptide hormones and their cognate receptors belonging to neuropeptide Y (NPY) family mediate diverse biological functions in a number of tissues. Recently, we discovered the presence of the gut satiation peptide YY (PYY) in saliva of mice and humans and defined its role in the regulation of food intake and body weight maintenance. Here we report the systematic analysis of expression patterns of all NPY receptors (Rs), Y1R, Y2R, Y4R, and Y5R in lingual epithelia in mice. Using four independent assays, immunohistochemistry, in situ hybridization, immunocytochemistry and RT PCR, we show that the morphologically different layers of the keratinized stratified epithelium of the dorsal layer of the tongue express Y receptors in a very distinctive yet overlapping pattern. In particular, the monolayer of basal progenitor cells expresses both Y1 and Y2 receptors. Y1Rs are present in the parabasal prickle cell layer and the granular layer, while differentiated keratinocytes display abundant Y5Rs. Y4Rs are expressed substantially in the neuronal fibers innervating the lamina propria and mechanoreceptors. Basal epithelial cells positive for Y2Rs respond robustly to PYY(3-36) by increasing intracellular Ca(2+) suggesting their possible functional interaction with salivary PYY. In taste buds of the circumvallate papillae, some taste receptor cells (TRCs) express YRs localized primarily at the apical domain, indicative of their potential role in taste perception. Some of the YR-positive TRCs are co-localized with neuronal cell adhesion molecule (NCAM), suggesting that these TRCs may have synaptic contacts with nerve terminals. In summary, we show that all YRs are abundantly expressed in multiple lingual cell types, including epithelial progenitors, keratinocytes, neuronal dendrites and TRCs. These results suggest that these receptors may be involved in the mediation of a wide variety of functions, including proliferation, differentiation, motility, taste perception and satiation.
- Published
- 2012
- Full Text
- View/download PDF
14. Glucagon signaling modulates sweet taste responsiveness.
- Author
-
Elson AE, Dotson CD, Egan JM, and Munger SD
- Subjects
- Animals, Base Sequence, Behavior, Animal, DNA Primers, Mice, Mice, Inbred C57BL, Receptors, Glucagon metabolism, Reverse Transcriptase Polymerase Chain Reaction, Taste Buds cytology, Taste Buds physiology, Glucagon metabolism, Signal Transduction, Taste
- Abstract
The gustatory system provides critical information about the quality and nutritional value of food before it is ingested. Thus, physiological mechanisms that modulate taste function in the context of nutritional needs or metabolic status could optimize ingestive decisions. We report that glucagon, which plays important roles in the maintenance of glucose homeostasis, enhances sweet taste responsiveness through local actions in the mouse gustatory epithelium. Using immunohistochemistry and confocal microscopy, we found that glucagon and its receptor (GlucR) are coexpressed in a subset of mouse taste receptor cells. Most of these cells also express the T1R3 taste receptor implicated in sweet and/or umami taste. Genetic or pharmacological disruption of glucagon signaling in behaving mice indicated a critical role for glucagon in the modulation of taste responsiveness. Scg5(-/-) mice, which lack mature glucagon, had significantly reduced responsiveness to sucrose as compared to wild-type littermates in brief-access taste tests. No significant differences were seen in responses to prototypical salty, sour, or bitter stimuli. Taste responsiveness to sucrose was similarly reduced upon acute and local disruption of glucagon signaling by the GlucR antagonist L-168,049. Together, these data indicate a role for local glucagon signaling in the peripheral modulation of sweet taste responsiveness.
- Published
- 2010
- Full Text
- View/download PDF
15. The search for mechanisms underlying the sour taste evoked by acids continues.
- Author
-
Dotson CD
- Subjects
- Animals, Mice, Mice, Knockout, Protein Kinase C metabolism, Acids metabolism, Taste physiology, Taste Buds metabolism
- Abstract
It has been postulated for decades that ion channels serve as receptors for most sour tasting stimuli. Though many candidates exist, definitive evidence linking any particular channel to sour taste perception has been elusive. Several studies have suggested that two members of the polycystic kidney disease-like family may function as components of an ionotropic taste receptor mediating the transduction of acids. However, the precise role of these proteins in sour taste is controversial. In this issue of Chemical Senses, Nelson et al. use behavioral and electrophysiological approaches in gene-targeted mice to show that one of these putative sour taste receptor subunits, Pkd1l3, is unnecessary for normal taste responses to acids. Their results suggest that other mechanisms and/or other candidate receptors must be contributing to the transduction of acids and the subsequent perception of sour taste.
- Published
- 2010
- Full Text
- View/download PDF
16. T1R and T2R receptors: the modulation of incretin hormones and potential targets for the treatment of type 2 diabetes mellitus.
- Author
-
Dotson CD, Vigues S, Steinle NI, and Munger SD
- Subjects
- Animals, Diabetes Mellitus, Type 2 metabolism, Glucose metabolism, Glucose therapeutic use, Humans, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents therapeutic use, Incretins therapeutic use, Insulin therapeutic use, Receptors, G-Protein-Coupled metabolism
- Abstract
Type 2 diabetes mellitus (T2DM), which is characterized by insulin and glucose dysregulation, is a major contributor to the development of cardiovascular disease, renal failure and premature death. Incretin hormones are released from the intestines upon nutrient ingestion and contribute to glucose homeostasis in part by promoting insulin secretion from the pancreas. Drugs that enhance the incretin response have emerged as effective treatments for T2DM. Several recent studies have revealed that incretin secretion from enteroendocrine cells in the intestines can be modulated by T1R and T2R receptors, proteins that have been demonstrated to function as taste receptors. This review focuses on the intriguing finding that taste receptors may be involved in modulating the incretin response, and considers T1Rs and T2Rs as potential targets for new hypoglycemic drugs.
- Published
- 2010
17. Variation in the gene TAS2R38 is associated with the eating behavior disinhibition in Old Order Amish women.
- Author
-
Dotson CD, Shaw HL, Mitchell BD, Munger SD, and Steinle NI
- Subjects
- Diet methods, Diet statistics & numerical data, Female, Genetic Variation genetics, Humans, Hunger physiology, Inhibition, Psychological, Male, Middle Aged, Pennsylvania, Protestantism, Sex Factors, Surveys and Questionnaires, Taste genetics, Feeding Behavior, Hyperphagia genetics, Polymorphism, Single Nucleotide genetics, Receptors, G-Protein-Coupled genetics
- Abstract
Insensitivity to the bitter-tasting compound 6-n-propylthiouracil (PROP) has been proposed as a marker for individual differences in taste perception that influence food preference and intake. The principal genetic determinants of phenotypic variation in PROP taste sensitivity are alleles of the TAS2R38 gene, which encodes a chemosensory receptor sensitive to thiourea compounds including PROP and phenylthiocarbamide. Members of the TAS2R family are expressed in the gustatory system, where they function as bitter taste receptors, and throughout the gut, where their physiological roles in prandial, gut-derived hormone release are beginning to be elucidated. To better understand the relationship between TAS2R function and ingestive behaviors, we asked if TAS2R38 variants are associated with one or more of three eating behaviors: restraint, disinhibition, and hunger. We genotyped a single nucleotide polymorphism (SNP) located within the TAS2R38 gene, rs1726866 (T785C, Val262Ala) in 729 nondiabetic individuals (381 females, 348 males) within the Amish Family Diabetes Study. Eating behaviors were assessed using the Three-Factor Eating Questionnaire. An association analysis between rs1726866 and these three traits revealed a significant association of the PROP-insensitive "T" allele with increased disinhibition (p=0.03). Because eating behaviors differ substantially between males and females, we subsequently performed sex-stratified analyses, which revealed a strong association in females (p=0.0002) but not in males. Analyses with other SNPs in close proximity to rs1726866 suggest that this locus is principally responsible for the association. Therefore, our results indicate that a polymorphism in TAS2R38 is associated with differences in ingestive behavior., (2009 Elsevier Ltd. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
18. Modulation of taste sensitivity by GLP-1 signaling in taste buds.
- Author
-
Martin B, Dotson CD, Shin YK, Ji S, Drucker DJ, Maudsley S, and Munger SD
- Subjects
- Animals, Glucagon-Like Peptide-1 Receptor, Mice, Mice, Knockout, Receptors, Glucagon genetics, Receptors, Glucagon metabolism, Receptors, Glucagon physiology, Glucagon-Like Peptide 1 metabolism, Signal Transduction, Taste, Taste Buds metabolism
- Abstract
Modulation of sensory function can help animals adjust to a changing external and internal environment. Even so, mechanisms for modulating taste sensitivity are poorly understood. Using immunohistochemical, biochemical, and behavioral approaches, we found that the peptide hormone glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) are expressed in mammalian taste buds. Furthermore, we found that GLP-1 signaling plays an important role in the modulation of taste sensitivity: GLP-1R knockout mice exhibit a dramatic reduction in sweet taste sensitivity as well as an enhanced sensitivity to umami-tasting stimuli. Together, these findings suggest a novel paracrine mechanism for the hormonal modulation of taste function in mammals.
- Published
- 2009
- Full Text
- View/download PDF
19. The receptor basis of sweet taste in mammals.
- Author
-
Vigues S, Dotson CD, and Munger SD
- Subjects
- Animals, Glucose metabolism, Glucose pharmacology, Humans, Mammals metabolism, Receptors, G-Protein-Coupled metabolism, Sucrose metabolism, Sucrose pharmacology, Sweetening Agents pharmacology, Taste Buds drug effects, Taste Buds metabolism, Taste Buds physiology, Taste Perception drug effects, Mammals physiology, Receptors, G-Protein-Coupled physiology, Sweetening Agents metabolism, Taste Perception physiology
- Abstract
The taste of sweeteners is hedonically pleasing, suggests high caloric value in food, and contributes to increased intake. In recent years, many of the molecular mechanisms underlying the detection of sweeteners have been elucidated. Of particular note is the identification of the sweet taste receptor, the heteromeric G-protein-coupled receptor T1R2:T1R3, which responds to a vast array of chemically diverse natural and artificial sweeteners. In this chapter, we discuss some of the mechanisms underlying the detection of sweeteners by mammals, with a particular focus on the function and role of the T1R2:T1R3 receptor in these processes.
- Published
- 2009
- Full Text
- View/download PDF
20. Modulation of taste sensitivity by GLP-1 signaling.
- Author
-
Shin YK, Martin B, Golden E, Dotson CD, Maudsley S, Kim W, Jang HJ, Mattson MP, Drucker DJ, Egan JM, and Munger SD
- Subjects
- Animals, Citric Acid pharmacology, Epithelial Cells cytology, Epithelial Cells drug effects, Glucagon-Like Peptide-1 Receptor, Macaca, Mice, Mice, Knockout, Rats, Rats, Sprague-Dawley, Sensory Receptor Cells cytology, Sensory Receptor Cells drug effects, Sensory Thresholds drug effects, Sensory Thresholds physiology, Signal Transduction physiology, Sweetening Agents pharmacology, Taste Buds cytology, Taste Buds drug effects, Visceral Afferents cytology, Visceral Afferents drug effects, Visceral Afferents metabolism, Epithelial Cells metabolism, Glucagon-Like Peptide 1 metabolism, Receptors, Glucagon genetics, Sensory Receptor Cells metabolism, Taste genetics, Taste Buds metabolism
- Abstract
In many sensory systems, stimulus sensitivity is dynamically modulated through mechanisms of peripheral adaptation, efferent input, or hormonal action. In this way, responses to sensory stimuli can be optimized in the context of both the environment and the physiological state of the animal. Although the gustatory system critically influences food preference, food intake and metabolic homeostasis, the mechanisms for modulating taste sensitivity are poorly understood. In this study, we report that glucagon-like peptide-1 (GLP-1) signaling in taste buds modulates taste sensitivity in behaving mice. We find that GLP-1 is produced in two distinct subsets of mammalian taste cells, while the GLP-1 receptor is expressed on adjacent intragemmal afferent nerve fibers. GLP-1 receptor knockout mice show dramatically reduced taste responses to sweeteners in behavioral assays, indicating that GLP-1 signaling normally acts to maintain or enhance sweet taste sensitivity. A modest increase in citric acid taste sensitivity in these knockout mice suggests GLP-1 signaling may modulate sour taste, as well. Together, these findings suggest a novel paracrine mechanism for the regulation of taste function.
- Published
- 2008
- Full Text
- View/download PDF
21. Bitter taste receptors influence glucose homeostasis.
- Author
-
Dotson CD, Zhang L, Xu H, Shin YK, Vigues S, Ott SH, Elson AE, Choi HJ, Shaw H, Egan JM, Mitchell BD, Li X, Steinle NI, and Munger SD
- Subjects
- Adult, Aged, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 metabolism, Enteroendocrine Cells metabolism, Family, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Linkage Disequilibrium, Middle Aged, Polymorphism, Single Nucleotide, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Taste Perception genetics, Taste Perception physiology, Glucose metabolism, Homeostasis genetics, Receptors, G-Protein-Coupled physiology
- Abstract
TAS1R- and TAS2R-type taste receptors are expressed in the gustatory system, where they detect sweet- and bitter-tasting stimuli, respectively. These receptors are also expressed in subsets of cells within the mammalian gastrointestinal tract, where they mediate nutrient assimilation and endocrine responses. For example, sweeteners stimulate taste receptors on the surface of gut enteroendocrine L cells to elicit an increase in intracellular Ca(2+) and secretion of the incretin hormone glucagon-like peptide-1 (GLP-1), an important modulator of insulin biosynthesis and secretion. Because of the importance of taste receptors in the regulation of food intake and the alimentary responses to chemostimuli, we hypothesized that differences in taste receptor efficacy may impact glucose homeostasis. To address this issue, we initiated a candidate gene study within the Amish Family Diabetes Study and assessed the association of taste receptor variants with indicators of glucose dysregulation, including a diagnosis of type 2 diabetes mellitus and high levels of blood glucose and insulin during an oral glucose tolerance test. We report that a TAS2R haplotype is associated with altered glucose and insulin homeostasis. We also found that one SNP within this haplotype disrupts normal responses of a single receptor, TAS2R9, to its cognate ligands ofloxacin, procainamide and pirenzapine. Together, these findings suggest that a functionally compromised TAS2R receptor negatively impacts glucose homeostasis, providing an important link between alimentary chemosensation and metabolic disease.
- Published
- 2008
- Full Text
- View/download PDF
22. Behavioral discrimination between sucrose and other natural sweeteners in mice: implications for the neural coding of T1R ligands.
- Author
-
Dotson CD and Spector AC
- Subjects
- Animals, Discrimination, Psychological drug effects, Ligands, Mice, Nerve Net drug effects, Receptors, G-Protein-Coupled physiology, Sucrose metabolism, Sweetening Agents metabolism, Taste drug effects, Taste physiology, Discrimination, Psychological physiology, Nerve Net metabolism, Receptors, G-Protein-Coupled metabolism, Sucrose administration & dosage, Sweetening Agents administration & dosage
- Abstract
In taste bud cells, two different T1R heteromeric taste receptors mediate signal transduction of sugars (the canonical "sweet" taste receptor, T1R2 + T1R3) and L-amino acids (the T1R1 + T1R3 receptor). The T1R1 + T1R3 receptor is thought to mediate what is considered the fifth basic taste quality "umami." However, a subset of L-amino acids is "sweet tasting" to humans and appears to possess a "sucrose-like" taste quality to nonhuman mammals. This suggests, to varying degrees, that all of these compounds activate a single neural channel that leads to the perception of sweetness. The experiments detailed here were designed to test the ability of mice to distinguish between sucrose and various others sugars and L-amino acids in operant taste discrimination tasks. Mice had at least some difficulty discriminating sucrose from L-serine, L-threonine, maltose, fructose, and glucose. For example, when concentration effects are taken into consideration, mice discriminated poorly, if at all, sucrose from glucose or fructose and, to a lesser extent maltose, suggesting that sugars generate a unitary perceptual quality. However, mice were able to reliably discriminate sucrose from L-serine and L-threonine. Data gathered using a conditioned taste aversion assay also suggest that, although qualitatively similar to the taste of sucrose, L-serine and L-threonine generate distinctive percepts. In conclusion, it appears that some signals from taste receptor proteins binding with sugars and some L-amino acids converge somewhere along the gustatory neuraxis. However, the results of these experiments also imply that sweet-tasting L-amino acids may possess qualitative taste characteristics that are distinguishable from the prototypical sweetener sucrose.
- Published
- 2007
- Full Text
- View/download PDF
23. PLCbeta2-independent behavioral avoidance of prototypical bitter-tasting ligands.
- Author
-
Dotson CD, Roper SD, and Spector AC
- Subjects
- Animals, Dose-Response Relationship, Drug, Ligands, Mice, Mice, Knockout, Nerve Tissue Proteins deficiency, Phosphoinositide Phospholipase C, Quaternary Ammonium Compounds administration & dosage, Quinine administration & dosage, Sensory Thresholds, Signal Transduction, Stimulation, Chemical, Sucrose administration & dosage, Type C Phospholipases deficiency, Avoidance Learning physiology, Nerve Tissue Proteins physiology, Taste, Type C Phospholipases physiology
- Abstract
Using a brief-access taste assay, we show in the present report that although phospholipase C beta2 knockout (PLCbeta2 KO) mice are unresponsive to low- and midrange concentrations of quinine and denatonium, they do significantly avoid licking higher concentrations of these aversive compounds. PLCbeta2 KO mice displayed no concentration-dependent licking of the prototypical sweetener sucrose but were similar to wild-type mice in their responses to citric acid and NaCl, notwithstanding some interesting exceptions. Although these findings confirm an essential role for PLCbeta2 in taste responsiveness to sucrose and to low- to midrange concentrations of quinine and denatonium in mice as previously reported, they importantly suggest that higher concentrations of the latter two compounds, which are bitter to humans, can engage a PLCbeta2-independent taste transduction pathway.
- Published
- 2005
- Full Text
- View/download PDF
24. Drinking spout orifice size affects licking behavior in inbred mice.
- Author
-
Dotson CD and Spector AC
- Subjects
- Animals, Equipment Design, Male, Mice, Mice, Inbred Strains, Time Factors, Drinking Behavior, Physiology instrumentation
- Abstract
Using a lickometer, we assessed the effect of drinking spout orifice size on the licking behavior of inbred mice [C57BL/6J, SWR/J, 129P3/J and DBA/2J]. Animals licked from drinking spout sipper tubes that had what were defined as either a large (2.7 mm) or a small (1.5 mm) orifice. Mice took approximately twice as many licks from a stationary single small orifice drinking spout than when licking from a spout with a large orifice during separate 30-min sessions. However, their total intake volume was approximately the same. We calculated that mice received a mean of 0.55 muL per lick from the drinking tubes with a small orifice and a mean of 1.15 muL per lick from the drinking tubes with a large orifice. Thus, the animals appear to have regulated their fluid intake by proportionally adjusting their licking as a function of the lick volume. On average, this regulation occurred through modulation of the size of licking bursts and not their frequency. However, strain differences in compensation strategy were observed. When licking was restricted to a series of 5-s trials in a 30-min brief access test session, the smaller orifice size increased the range of responsiveness that was expressed. Mice increased their average licks per trial by 20% and took 60% more trials when licking from a spout with a small orifice. Interestingly, when the orifice size was quasi-randomly varied within a brief access session, licking was greater from large orifice drinking spouts, suggesting that water delivered from the two orifice sizes differs in its reinforcement efficacy. These findings demonstrate that drinking spout orifice size can significantly influence experimental outcomes in licking tests involving mice and care should be taken in controlling this variable in testing the effects of taste or other factors on ingestive behavior.
- Published
- 2005
- Full Text
- View/download PDF
25. The relative affective potency of glycine, L-serine and sucrose as assessed by a brief-access taste test in inbred strains of mice.
- Author
-
Dotson CD and Spector AC
- Subjects
- Animals, Dose-Response Relationship, Drug, Food Preferences, Glycine administration & dosage, Male, Mice, Mice, Inbred Strains, Receptors, G-Protein-Coupled metabolism, Serine administration & dosage, Species Specificity, Sucrose administration & dosage, Sweetening Agents administration & dosage, Taste Buds physiology, Glycine pharmacology, Serine pharmacology, Sucrose pharmacology, Sweetening Agents pharmacology, Taste genetics
- Abstract
In general, rodents prefer both sucrose and L-serine relative to water and treat both compounds as possessing a similar taste quality (e.g. 'sweetness') despite that they are believed to bind with different T1R heterodimeric receptors in taste bud cells. We assessed the affective potency of these compounds along with glycine, which is thought to bind with both T1R receptor complexes, using a brief-access taste test in a gustometer. Unconditioned licking responses of two 'taster' strains (C57BL/6J and SWR/J), which display high preference for low concentrations of sucrose, and two 'non-taster' (129P3/J and DBA/2J) strains, which display blunted preference for low concentrations of sucrose, were measured during 5 s trials of varying concentrations of a single compound when mice (n=10/strain/stimulus) were non-deprived and when access to home-cage water was restricted. In non-deprived mice, sucrose generated monotonically increasing concentration-response curves regardless of strain, whereas glycine was only marginally effective at stimulating licking and L-serine produced relatively flat functions. The profile of responsiveness across strains was more complex than expected. For example, when tested with sucrose in the non-deprived condition, the 129P3/J non-taster strain surpassed the responsiveness of taster mice at mid-range to high concentrations. Under water-restricted conditions, these mice also were significantly more responsive to high concentrations of both sucrose and glycine compared with the other strains when stimulus licking was standardized relative to water. Thus, the affective potency of the stimuli tested here seems to be related to the ability of the compounds to bind with the T1R2+3 receptor complex. However, the profile of strain responsiveness to these tastants in the brief-access test does not appear to be simply explained by the sweetener 'taster' status of the strain.
- Published
- 2004
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.