45 research outputs found

    Bitter Taste Receptors Influence Glucose Homeostasis

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    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 Ca2+ 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

    Potential therapeutic approaches for modulating expression and accumulation of defective lamin A in laminopathies and age-related diseases

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    Characterization of Obese Individuals who Claim to Detect no Relationship between their Eating Pattern and Sensations of Hunger or Fullness

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    OBJECTIVE: To study the phenomenon that obese subjects show considerable individual variability in their reported relationships between eating and sensations of hunger and fullness. DESIGN: A laboratory study of the relationship between eating behaviour traits and the episodic oscillations in sensations of hunger and fullness in response to obligatory, fixed energy breakfast (481 kcal) and lunch (675 kcal) meals. SUBJECTS: Obese subjects were divided into two groups based on their responses to four 'screening' questions associated with their habitual experience of hunger and fullness sensations before and after eating: those who experienced sensations of hunger and fullness related to eating (Related-R; n=20, body mass index (BMI)=42.4 kg/m(2)) and those for whom eating was not related to hunger or fullness sensations (Unrelated - UR; n=19, BMI=41.3 kg/m(2)). In addition, a control, lean group (Control - C; n=14, BMI=22.6 kg/m(2)) who experienced sensations of hunger and fullness related to eating was studied. MEASUREMENTS: The Three-Factor Eating Questionnaire (TFEQ) was used to measure the eating behaviour traits, disinhibition, restraint and hunger. Profiles of subjective appetite sensations were continuously monitored across the day using visual analogue scales. RESULTS: All groups displayed clear meal-related oscillations in subjective sensations of hunger, fullness, desire to eat and prospective consumption. In contrast, the TFEQ disinhibition and hunger scores (but not restraint scores) were significantly different (P<0.05) between the groups ((UR; D=13.5+/-0.5, H=10.0+/-0.5), R (D 7.5+/-0.6, H 6.1+/-0.4), C(D 3.7+/-0.5, H 3.7+/-0.5)). In addition, analysis of the intra-meal changes in subjective appetite sensations revealed that the UR group displayed a smaller meal-induced suppression of hunger and elevation of fullness. CONCLUSION: These data indicate that the reported relationship between eating and hunger/fullness was associated with obese individuals showing high or low disinhibition scores. In addition, the data suggest that the processes underlying disinhibition may be associated with a modulation of the recognition of meal-related satiety sensations
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