scholarly journals 3-Deoxyglucosone Induces Glucagon-Like Peptide-1 Secretion from STC-1 Cells via Upregulating Sweet Taste Receptor Expression under Basal Conditions

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Xiudao Song ◽  
Fei Wang ◽  
Heng Xu ◽  
Guoqiang Liang ◽  
Liang Zhou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Transient Receptor Potential ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Receptor Expression ◽  
Oral Glucose ◽  
Intragastric Administration ◽  
Sweet Taste Receptor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

3-Deoxyglucosone (3DG) is derived from D-glucose during food processing and storage and under physiological conditions. We reported that glucagon-like peptide-1 (GLP-1) secretion in response to an oral glucose load in vivo and high-glucose stimulation in vitro was decreased by acute 3DG administration. In this study, we determined the acute effect of 3DG on GLP-1 secretion under basal conditions and investigated the possible mechanisms. Normal fasting rats were given a single acute intragastric administration of 50 mg/kg 3DG. Plasma basal GLP-1 levels and duodenum 3DG content and sweet taste receptor expression were measured. STC-1 cells were acutely exposed to 3DG (80, 300, and 1000 ng/ml) for 1 h under basal conditions (5.6 mM glucose), and GLP-1 secretion, intracellular concentrations of cyclic adenosine monophosphate (cAMP) and Ca2+, and molecular expression of STR signaling pathway were measured. Under the fasted state, plasma GLP-1 levels, duodenum 3DG content, and duodenum STR expression were elevated in 3DG-treated rats. GLP-1 secretion was increased in 3DG-treated cells under either 5.6 mM glucose or glucose-free conditions. 3DG-induced acute GLP-1 secretion from STC-1 cells under 5.6 mM glucose was inhibited in the presence of the STR inhibitor lactisole, which was consistent with the observation under glucose-free conditions. Moreover, acute exposure to 3DG increased the protein expression of TAS1R2 and TAS1R3 under either 5.6 mM glucose or glucose-free conditions, with affecting other components of STR signaling pathway, including the upregulation of transient receptor potential channel type M5 TRPM5 and the increment of intracellular Ca2+ concentration. In summary, the glucose-free condition was used to first demonstrate the involvement of STR in 3DG-induced acute GLP-1 secretion. These results first showed that acute 3DG administration induces basal GLP-1 secretion in part through upregulation of STR expression.

scholarly journals Evidence that human oral glucose detection involves a sweet taste pathway and a glucose transporter pathway

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0256989
Author(s):  
Paul A. S. Breslin ◽  
Akiko Izumi ◽  
Anilet Tharp ◽  
Tadahiro Ohkuri ◽  
Yoshiaki Yokoo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Glucose Transporter ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Oral Glucose ◽  
Glucose Detection ◽  
Detection Thresholds ◽  
Glucose Signaling ◽  
Sweet Taste Receptor ◽  
Class 1

The taste stimulus glucose comprises approximately half of the commercial sugar sweeteners used today, whether in the form of the di-saccharide sucrose (glucose-fructose) or half of high-fructose corn syrup (HFCS). Therefore, oral glucose has been presumed to contribute to the sweet taste of foods when combined with fructose. In light of recent rodent data on the role of oral metabolic glucose signaling, we examined psychopharmacologically whether oral glucose detection may also involve an additional pathway in humans to the traditional sweet taste transduction via the class 1 taste receptors T1R2/T1R3. In a series of experiments, we first compared oral glucose detection thresholds to sucralose thresholds without and with addition of the T1R receptor inhibitor Na-lactisole. Next, we compared oral detection thresholds of glucose to sucralose and to the non-metabolizable glucose analog, α-methyl-D-glucopyranoside (MDG) without and with the addition of the glucose co-transport component sodium (NaCl). Finally, we compared oral detection thresholds for glucose, MDG, fructose, and sucralose without and with the sodium-glucose co-transporter (SGLT) inhibitor phlorizin. In each experiment, psychopharmacological data were consistent with glucose engaging an additional signaling pathway to the sweet taste receptor T1R2/T1R3 pathway. Na-lactisole addition impaired detection of the non-caloric sweetener sucralose much more than it did glucose, consistent with glucose using an additional signaling pathway. The addition of NaCl had a beneficial impact on the detection of glucose and its analog MDG and impaired sucralose detection, consistent with glucose utilizing a sodium-glucose co-transporter. The addition of the SGLT inhibitor phlorizin impaired detection of glucose and MDG more than it did sucralose, and had no effect on fructose, further evidence consistent with glucose utilizing a sodium-glucose co-transporter. Together, these results support the idea that oral detection of glucose engages two signaling pathways: one that is comprised of the T1R2/T1R3 sweet taste receptor and the other that utilizes an SGLT glucose transporter.

scholarly journals Transformation of postingestive glucose responses after deletion of sweet taste receptor subunits or gastric bypass surgery

2012 ◽  
Vol 303 (4) ◽  
pp. E464-E474 ◽  
Author(s):  
Maartje C. P. Geraedts ◽  
Tatsuyuki Takahashi ◽  
Stephan Vigues ◽  
Michele L. Markwardt ◽  
Andongfac Nkobena ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Glycemic Control ◽  
Large Intestine ◽  
Molecular Mechanisms ◽  
Hormone Secretion ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Oral Glucose ◽  
Isolated Pancreatic Islets ◽  
Sweet Taste Receptor

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+(KATP) 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 KATPchannel 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 KATPchannel-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.

scholarly journals Sweet taste receptor expression in ruminant intestine and its activation by artificial sweeteners to regulate glucose absorption

2014 ◽  
Vol 97 (8) ◽  
pp. 4955-4972 ◽  
Author(s):  
A.W. Moran ◽  
M. Al-Rammahi ◽  
C. Zhang ◽  
D. Bravo ◽  
S. Calsamiglia ◽  
...  
Keyword(s):  
Taste Receptor ◽  
Sweet Taste ◽  
Glucose Absorption ◽  
Receptor Expression ◽  
Artificial Sweeteners ◽  
Sweet Taste Receptor

scholarly journals Sweet Taste Is Complex: Signaling Cascades and Circuits Involved in Sweet Sensation

2021 ◽  
Vol 15 ◽  
Author(s):  
Elena von Molitor ◽  
Katja Riedel ◽  
Michael Krohn ◽  
Mathias Hafner ◽  
Rüdiger Rudolf ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Taste Receptor ◽  
Physiological Role ◽  
Primary Source ◽  
Sweet Taste ◽  
Receptor Expression ◽  
Taste Bud ◽  
Sweet Taste Receptor ◽  
The Brain ◽  
Taste Bud Cells

Sweetness is the preferred taste of humans and many animals, likely because sugars are a primary source of energy. In many mammals, sweet compounds are sensed in the tongue by the gustatory organ, the taste buds. Here, a group of taste bud cells expresses a canonical sweet taste receptor, whose activation induces Ca2+ rise, cell depolarization and ATP release to communicate with afferent gustatory nerves. The discovery of the sweet taste receptor, 20 years ago, was a milestone in the understanding of sweet signal transduction and is described here from a historical perspective. Our review briefly summarizes the major findings of the canonical sweet taste pathway, and then focuses on molecular details, about the related downstream signaling, that are still elusive or have been neglected. In this context, we discuss evidence supporting the existence of an alternative pathway, independent of the sweet taste receptor, to sense sugars and its proposed role in glucose homeostasis. Further, given that sweet taste receptor expression has been reported in many other organs, the physiological role of these extraoral receptors is addressed. Finally, and along these lines, we expand on the multiple direct and indirect effects of sugars on the brain. In summary, the review tries to stimulate a comprehensive understanding of how sweet compounds signal to the brain upon taste bud cells activation, and how this gustatory process is integrated with gastro-intestinal sugar sensing to create a hedonic and metabolic representation of sugars, which finally drives our behavior. Understanding of this is indeed a crucial step in developing new strategies to prevent obesity and associated diseases.

311 Altered Duodenal Sweet Taste Receptor Expression in Diabetic Hyperglycemia

2008 ◽  
Vol 134 (4) ◽  
pp. A-44
Author(s):  
Kate Sutherland ◽  
Stuart M. Brierley ◽  
Chris Rayner ◽  
Michael Horowitz ◽  
L. Ashley Blackshaw ◽  
...  
Keyword(s):  
Taste Receptor ◽  
Sweet Taste ◽  
Receptor Expression ◽  
Sweet Taste Receptor

scholarly journals Critically evaluating sweet taste receptor expression and signaling through a molecular pharmacology lens

FEBS Journal ◽  
2021 ◽  
Vol 288 (8) ◽  
pp. 2660-2672 ◽  
Author(s):  
Nicola J. Smith ◽  
Jennifer N. Grant ◽  
Justin I. Moon ◽  
Sean S. So ◽  
Angela M. Finch
Keyword(s):  
Taste Receptor ◽  
Sweet Taste ◽  
Receptor Expression ◽  
Molecular Pharmacology ◽  
Sweet Taste Receptor

scholarly journals Intestinal alteration of a-gustducin and sweet taste signaling pathway in metabolic diseases is partly rescued after weight loss and diabetes remission

2021 ◽  
Author(s):  
Léa Le Gléau ◽  
Christine Rouault ◽  
Céline Osinski ◽  
Edi Prifti ◽  
Hédi Antoine Soula ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
G Protein ◽  
Metabolic Diseases ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Fecal Microbiota ◽  
Diabetes Remission ◽  
Sweet Taste Receptor ◽  
A Subunit ◽  
Altered Gene

Carbohydrates and sweeteners are detected by the sweet taste receptor in enteroendocrine cells (EEC). This receptor is coupled to the gustducin G-protein, which a-subunit is encoded by GNAT3 gene. In intestine, the activation of sweet taste receptor triggers a signaling pathway leading to GLP-1 secretion, an incretin hormone. In metabolic diseases GLP-1 concentration and incretin effect are reduced while partly restored after Roux-en-Y gastric bypass (RYGB). We wondered if the decreased GLP-1 secretion in metabolic diseases is caused by an intestinal defect in sweet taste transduction pathway. In our RNA-sequencing of EEC GNAT3 expression is decreased in patients with obesity and type 2 diabetes compared to normoglycemic obese patients. This prompted us to explore sweet taste signaling pathway in mice with metabolic deteriorations. During obesity onset in mice Gnat3 expression was downregulated in EEC. After metabolic improvement with entero-gastro anastomosis surgery in mice (a surrogate of the RYGB in humans), the expression of Gnat3 increased in the new alimentary tract and glucose-induced GLP-1 secretion was improved. In order to evaluate if high-fat diet-induced dysbiotic intestinal microbiota could explain the changes in the expression of sweet taste a-subunit G protein, we performed a fecal microbiota transfer in mice. However, we could not conclude if dysbiotic microbiota impacted or not intestinal Gnat3 expression. Our data highlight that metabolic disorders were associated with altered gene expression of sweet taste signaling in intestine. This could contribute to impaired GLP-1 secretion that is partly rescued after metabolic improvement.

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