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Anthony Sclafani - One of the best experts on this subject based on the ideXlab platform.
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Glucose elicits Cephalic-Phase insulin release in mice by activating KATP channels in taste cells.
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2017Co-Authors: John I. Glendinning, Gabrielle S. Lubitz, Yonina G. Frim, Ayelet Hochman, Anthony J. Basile, Anthony SclafaniAbstract:The taste of sugar elicits Cephalic-Phase insulin release (CPIR), which limits the rise in blood glucose associated with meals. Little is known, however, about the gustatory mechanisms that trigger CPIR. We asked whether oral stimulation with any of the following taste stimuli elicited CPIR in mice: glucose, sucrose, maltose, fructose, Polycose, saccharin, sucralose, AceK, SC45647, or a nonmetabolizable sugar analog. The only taste stimuli that elicited CPIR were glucose and the glucose-containing saccharides (sucrose, maltose, Polycose). When we mixed an α-glucosidase inhibitor (acarbose) with the latter three saccharides, the mice no longer exhibited CPIR. This revealed that the carbohydrates were hydrolyzed in the mouth, and that the liberated glucose triggered CPIR. We also found that increasing the intensity or duration of oral glucose stimulation caused a corresponding increase in CPIR magnitude. To identify the components of the glucose-specific taste-signaling pathway, we examined the necessity of Calhm1, P2X2+P2X3, SGLT1, and Sur1. Among these proteins, only Sur1 was necessary for CPIR. Sur1 was not necessary, however, for taste-mediated attraction to sugars. Given that Sur1 is a subunit of the ATP-sensitive K+ channel (KATP) channel and that this channel functions as a part of a glucose-sensing pathway in pancreatic β-cells, we asked whether the KATP channel serves an analogous role in taste cells. We discovered that oral stimulation with drugs known to increase (glyburide) or decrease (diazoxide) KATP signaling produced corresponding changes in glucose-stimulated CPIR. We propose that the KATP channel is part of a novel signaling pathway in taste cells that mediates glucose-induced CPIR.
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Sugar-induced Cephalic-Phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2015Co-Authors: John I. Glendinning, Sarah Stano, Marlena M. Holter, Tali Azenkot, Olivia Goldman, Robert F. Margolskee, Joseph R. Vasselli, Anthony SclafaniAbstract:Sensory stimulation from foods elicits Cephalic Phase responses, which facilitate digestion and nutrient assimilation. One such response, Cephalic-Phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar.
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sugar induced Cephalic Phase insulin release is mediated by a t1r2 t1r3 independent taste transduction pathway in mice
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2015Co-Authors: John I. Glendinning, Sarah Stano, Marlena M. Holter, Tali Azenkot, Olivia Goldman, Robert F. Margolskee, Joseph R. Vasselli, Anthony SclafaniAbstract:Sensory stimulation from foods elicits Cephalic Phase responses, which facilitate digestion and nutrient assimilation. One such response, Cephalic-Phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar.
John I. Glendinning - One of the best experts on this subject based on the ideXlab platform.
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Taste of glucose elicits Cephalic-Phase insulin release in mice
Physiology & Behavior, 2018Co-Authors: John I. Glendinning, Gabrielle S. Lubitz, Sarah ShellingAbstract:Abstract We reported previously that when C57BL/6 (B6) mice ingest glucose, plasma insulin levels rise above baseline before blood glucose levels do so. This observation led us to speculate that the taste of glucose elicits Cephalic-Phase insulin release (CPIR) in mice. Here, we examined the specific contributions of taste and glucose to CPIR. In Experiment 1, we bypassed the mouth and delivered glucose directly to the stomach. We found that plasma insulin levels did not rise above baseline until after blood glucose levels did so. This revealed that taste stimulation is necessary for rapid insulin release (i.e., CPIR) in mice. In Experiment 2, we examined the observation that sucrose, maltose and Polycose (a maltodextrin) all elicit CPIR. We proposed in a prior study that these carbohydrates did not directly elicit CPIR; instead, they were digested by oral amylases and alpha-glucosidases, and that it was the enzymatically liberated glucose that elicited CPIR. In support of this possibility, we reported that acarbose (an alpha-glucosidase inhibitor) prevented sucrose, maltose and Polycose from eliciting CPIR. Here, we sought to confirm that glucose alone could elicit CPIR in the presence of acarbose. Indeed, we found that glucose alone and glucose+acarbose each elicited equally robust CPIR. Taken together, these results provide further support for the hypothesis that mice possess a glucose-specific taste transduction pathway that triggers rapid insulin release.
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Glucose elicits Cephalic-Phase insulin release in mice by activating KATP channels in taste cells.
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2017Co-Authors: John I. Glendinning, Gabrielle S. Lubitz, Yonina G. Frim, Ayelet Hochman, Anthony J. Basile, Anthony SclafaniAbstract:The taste of sugar elicits Cephalic-Phase insulin release (CPIR), which limits the rise in blood glucose associated with meals. Little is known, however, about the gustatory mechanisms that trigger CPIR. We asked whether oral stimulation with any of the following taste stimuli elicited CPIR in mice: glucose, sucrose, maltose, fructose, Polycose, saccharin, sucralose, AceK, SC45647, or a nonmetabolizable sugar analog. The only taste stimuli that elicited CPIR were glucose and the glucose-containing saccharides (sucrose, maltose, Polycose). When we mixed an α-glucosidase inhibitor (acarbose) with the latter three saccharides, the mice no longer exhibited CPIR. This revealed that the carbohydrates were hydrolyzed in the mouth, and that the liberated glucose triggered CPIR. We also found that increasing the intensity or duration of oral glucose stimulation caused a corresponding increase in CPIR magnitude. To identify the components of the glucose-specific taste-signaling pathway, we examined the necessity of Calhm1, P2X2+P2X3, SGLT1, and Sur1. Among these proteins, only Sur1 was necessary for CPIR. Sur1 was not necessary, however, for taste-mediated attraction to sugars. Given that Sur1 is a subunit of the ATP-sensitive K+ channel (KATP) channel and that this channel functions as a part of a glucose-sensing pathway in pancreatic β-cells, we asked whether the KATP channel serves an analogous role in taste cells. We discovered that oral stimulation with drugs known to increase (glyburide) or decrease (diazoxide) KATP signaling produced corresponding changes in glucose-stimulated CPIR. We propose that the KATP channel is part of a novel signaling pathway in taste cells that mediates glucose-induced CPIR.
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Sugar-induced Cephalic-Phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2015Co-Authors: John I. Glendinning, Sarah Stano, Marlena M. Holter, Tali Azenkot, Olivia Goldman, Robert F. Margolskee, Joseph R. Vasselli, Anthony SclafaniAbstract:Sensory stimulation from foods elicits Cephalic Phase responses, which facilitate digestion and nutrient assimilation. One such response, Cephalic-Phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar.
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sugar induced Cephalic Phase insulin release is mediated by a t1r2 t1r3 independent taste transduction pathway in mice
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2015Co-Authors: John I. Glendinning, Sarah Stano, Marlena M. Holter, Tali Azenkot, Olivia Goldman, Robert F. Margolskee, Joseph R. Vasselli, Anthony SclafaniAbstract:Sensory stimulation from foods elicits Cephalic Phase responses, which facilitate digestion and nutrient assimilation. One such response, Cephalic-Phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar.
Hong Yang - One of the best experts on this subject based on the ideXlab platform.
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TRH/TRH-R1 Receptor Signaling in the Brain Medulla as a Pathway of Vagally Mediated Gut Responses During the Cephalic Phase
Current Pharmaceutical Design, 2014Co-Authors: Yvette Taché, David W. Adelson, Hong YangAbstract:Pavlov’s seminal findings in the early twentieth century showed that the sight, smell or taste of food in dogs with chronic esophagostomy induces a vagal-dependent gastric acid secretion. These observations established the concept of the Cephalic Phase of digestion. Compelling experimental evidence in rats indicates that the three amino acid peptide thyrotropin-releasing hormone (TRH) expressed in the brainstem plays a key role in the vagal stimulation of gastric function. Neurons in the dorsal motor nucleus of the vagus (DMN) expressed TRH receptor subtype (TRH-R1) and received efferent input from TRH containing fibers arising from TRH synthesizing neurons in the raphe pallidus, raphe obscurus, and the parapyramidal regions. TRH microinjected into the DMN or intracisternally excites the firing of DMN neurons and stimulates efferent activity in the gastric branch of the vagus nerve and gastric myenteric cholinergic neurons. At the functional level, this results in a vagally-mediated and atropine-sensitive stimulation of gastric epithelial and endocrine cells secreting acid, pepsin, serotonin, histamine and ghrelin, and enteric neurons leading to increased gastric motility and emptying. Importantly, the blockade of TRH or TRH-R1 in the brainstem by pretreatment into the cisterna magna or the DMN with TRH antibody or TRH-R1 oligodeoxynucleotide antisense respectively abolishes the stimulation of gastric acid induced by sham-feeding. The gastric response to TRH injected into the DMN is potentiated by serotonin and the proTRH flanking peptide, Ps4 and suppressed by a number of brainstem peptides and cytokines activated during stress or immune response and inhibiting food intake and gastric acid secretion. These convergent data strongly support a physiological involvement of TRH signaling pathway in the brainstem to stimulate vagal activity and identified TRH-TRH-R1 system as a major effector in the dorsal vagal complex to drive the vagally mediated gut response triggered by the Cephalic Phase.
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trh trh r1 receptor signaling in the brain medulla as a pathway of vagally mediated gut responses during the Cephalic Phase
Current Pharmaceutical Design, 2014Co-Authors: Yvette Taché, David W. Adelson, Hong YangAbstract:Pavlov’s seminal findings in the early twentieth century showed that the sight, smell or taste of food in dogs with chronic esophagostomy induces a vagal-dependent gastric acid secretion. These observations established the concept of the Cephalic Phase of digestion. Compelling experimental evidence in rats indicates that the three amino acid peptide thyrotropin-releasing hormone (TRH) expressed in the brainstem plays a key role in the vagal stimulation of gastric function. Neurons in the dorsal motor nucleus of the vagus (DMN) expressed TRH receptor subtype (TRH-R1) and received efferent input from TRH containing fibers arising from TRH synthesizing neurons in the raphe pallidus, raphe obscurus, and the parapyramidal regions. TRH microinjected into the DMN or intracisternally excites the firing of DMN neurons and stimulates efferent activity in the gastric branch of the vagus nerve and gastric myenteric cholinergic neurons. At the functional level, this results in a vagally-mediated and atropine-sensitive stimulation of gastric epithelial and endocrine cells secreting acid, pepsin, serotonin, histamine and ghrelin, and enteric neurons leading to increased gastric motility and emptying. Importantly, the blockade of TRH or TRH-R1 in the brainstem by pretreatment into the cisterna magna or the DMN with TRH antibody or TRH-R1 oligodeoxynucleotide antisense respectively abolishes the stimulation of gastric acid induced by sham-feeding. The gastric response to TRH injected into the DMN is potentiated by serotonin and the proTRH flanking peptide, Ps4 and suppressed by a number of brainstem peptides and cytokines activated during stress or immune response and inhibiting food intake and gastric acid secretion. These convergent data strongly support a physiological involvement of TRH signaling pathway in the brainstem to stimulate vagal activity and identified TRH-TRH-R1 system as a major effector in the dorsal vagal complex to drive the vagally mediated gut response triggered by the Cephalic Phase.
Yvette Taché - One of the best experts on this subject based on the ideXlab platform.
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thyrotropin releasing hormone trh in the brainstem role of pavlov s vagally mediated Cephalic Phase of gastric secretion
Интегративная физиология, 2020Co-Authors: Yvette TachéAbstract:Pavlov’s seminal observation that sham feeding in dogs stimulates gastric acid secretion through the vagus nerve pioneered the concept of the Cephalic Phase of digestion. This has been subsequently extended to a wide range of mammals including humans. In the last decades, experimental evidence in rats established that the three amino acid peptide thyrotropinreleasing hormone (TRH) expressed in the brainstem plays a key role in the vagal stimulation of digestive secretory-motor function. The dorsal motor nucleus of the vagus (DMN) neurons expresses TRH receptor subtype 1 (TRH-R1) and receives input of TRH containing fibers arising from TRH synthesizing neurons in medullary raphe nuclei. The activation of TRHTRH-R1 signaling excites the firing of DMN neurons leading to the activation of vagal efferent discharges and gastric myenteric cholinergic neurons. This results in a vagally mediated and atropine-sensitive stimulation of gastric secretory and propulsive motor function, along with duodenal and pancreatic secretion. Importantly, the blockade of TRH or TRH-R1 in the brainstem inhibits the gastric acid response to sham feeding in rats. Collectively, these convergent data support the physiological relevance of medullary TRHTRH-R1 signaling as the end effector of the vagally mediated stimulation of digestive process in the Cephalic Phase.
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TRH/TRH-R1 Receptor Signaling in the Brain Medulla as a Pathway of Vagally Mediated Gut Responses During the Cephalic Phase
Current Pharmaceutical Design, 2014Co-Authors: Yvette Taché, David W. Adelson, Hong YangAbstract:Pavlov’s seminal findings in the early twentieth century showed that the sight, smell or taste of food in dogs with chronic esophagostomy induces a vagal-dependent gastric acid secretion. These observations established the concept of the Cephalic Phase of digestion. Compelling experimental evidence in rats indicates that the three amino acid peptide thyrotropin-releasing hormone (TRH) expressed in the brainstem plays a key role in the vagal stimulation of gastric function. Neurons in the dorsal motor nucleus of the vagus (DMN) expressed TRH receptor subtype (TRH-R1) and received efferent input from TRH containing fibers arising from TRH synthesizing neurons in the raphe pallidus, raphe obscurus, and the parapyramidal regions. TRH microinjected into the DMN or intracisternally excites the firing of DMN neurons and stimulates efferent activity in the gastric branch of the vagus nerve and gastric myenteric cholinergic neurons. At the functional level, this results in a vagally-mediated and atropine-sensitive stimulation of gastric epithelial and endocrine cells secreting acid, pepsin, serotonin, histamine and ghrelin, and enteric neurons leading to increased gastric motility and emptying. Importantly, the blockade of TRH or TRH-R1 in the brainstem by pretreatment into the cisterna magna or the DMN with TRH antibody or TRH-R1 oligodeoxynucleotide antisense respectively abolishes the stimulation of gastric acid induced by sham-feeding. The gastric response to TRH injected into the DMN is potentiated by serotonin and the proTRH flanking peptide, Ps4 and suppressed by a number of brainstem peptides and cytokines activated during stress or immune response and inhibiting food intake and gastric acid secretion. These convergent data strongly support a physiological involvement of TRH signaling pathway in the brainstem to stimulate vagal activity and identified TRH-TRH-R1 system as a major effector in the dorsal vagal complex to drive the vagally mediated gut response triggered by the Cephalic Phase.
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trh trh r1 receptor signaling in the brain medulla as a pathway of vagally mediated gut responses during the Cephalic Phase
Current Pharmaceutical Design, 2014Co-Authors: Yvette Taché, David W. Adelson, Hong YangAbstract:Pavlov’s seminal findings in the early twentieth century showed that the sight, smell or taste of food in dogs with chronic esophagostomy induces a vagal-dependent gastric acid secretion. These observations established the concept of the Cephalic Phase of digestion. Compelling experimental evidence in rats indicates that the three amino acid peptide thyrotropin-releasing hormone (TRH) expressed in the brainstem plays a key role in the vagal stimulation of gastric function. Neurons in the dorsal motor nucleus of the vagus (DMN) expressed TRH receptor subtype (TRH-R1) and received efferent input from TRH containing fibers arising from TRH synthesizing neurons in the raphe pallidus, raphe obscurus, and the parapyramidal regions. TRH microinjected into the DMN or intracisternally excites the firing of DMN neurons and stimulates efferent activity in the gastric branch of the vagus nerve and gastric myenteric cholinergic neurons. At the functional level, this results in a vagally-mediated and atropine-sensitive stimulation of gastric epithelial and endocrine cells secreting acid, pepsin, serotonin, histamine and ghrelin, and enteric neurons leading to increased gastric motility and emptying. Importantly, the blockade of TRH or TRH-R1 in the brainstem by pretreatment into the cisterna magna or the DMN with TRH antibody or TRH-R1 oligodeoxynucleotide antisense respectively abolishes the stimulation of gastric acid induced by sham-feeding. The gastric response to TRH injected into the DMN is potentiated by serotonin and the proTRH flanking peptide, Ps4 and suppressed by a number of brainstem peptides and cytokines activated during stress or immune response and inhibiting food intake and gastric acid secretion. These convergent data strongly support a physiological involvement of TRH signaling pathway in the brainstem to stimulate vagal activity and identified TRH-TRH-R1 system as a major effector in the dorsal vagal complex to drive the vagally mediated gut response triggered by the Cephalic Phase.
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Cephalic Phase of acid secretion involves activation of medullary TRH receptor subtype 1 in rats
American Journal of Physiology-gastrointestinal and Liver Physiology, 2002Co-Authors: Vicente Martinez, María Dolores Barrachina, Gordon V. Ohning, Yvette TachéAbstract:Mechanisms involved in the Cephalic Phase of gastric acid secretion were studied in awake fasted rats with chronic gastric fistula and exposed to the sight and smell of chow for 30 min. Acid secret...
Tali Azenkot - One of the best experts on this subject based on the ideXlab platform.
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Sugar-induced Cephalic-Phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2015Co-Authors: John I. Glendinning, Sarah Stano, Marlena M. Holter, Tali Azenkot, Olivia Goldman, Robert F. Margolskee, Joseph R. Vasselli, Anthony SclafaniAbstract:Sensory stimulation from foods elicits Cephalic Phase responses, which facilitate digestion and nutrient assimilation. One such response, Cephalic-Phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar.
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sugar induced Cephalic Phase insulin release is mediated by a t1r2 t1r3 independent taste transduction pathway in mice
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2015Co-Authors: John I. Glendinning, Sarah Stano, Marlena M. Holter, Tali Azenkot, Olivia Goldman, Robert F. Margolskee, Joseph R. Vasselli, Anthony SclafaniAbstract:Sensory stimulation from foods elicits Cephalic Phase responses, which facilitate digestion and nutrient assimilation. One such response, Cephalic-Phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar.