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Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.

Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Kojima I - PLoS ONE (2009)

Bottom Line: The effect of sucralose on [Ca(2+)](c) was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a G(q) inhibitor.Sucralose also induced sustained elevation of [cAMP](c), which was only partially inhibited by removal of extracellular calcium and nifedipine.Sweet taste receptor is expressed in beta-cells, and activation of this receptor induces insulin secretion by Ca(2+) and cAMP-dependent mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.

ABSTRACT

Background: Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets.

Methodology/principal findings: The expression of the sweet taste receptor was determined by RT-PCR and immunohistochemistry. Changes in cytoplasmic Ca(2+) ([Ca(2+)](c)) and cAMP ([cAMP](c)) were monitored in MIN6 cells using fura-2 and Epac1-camps. Activation of protein kinase C was monitored by measuring translocation of MARCKS-GFP. Insulin was measured by radioimmunoassay. mRNA for T1R2, T1R3, and gustducin was expressed in MIN6 cells. In these cells, artificial sweeteners such as sucralose, succharin, and acesulfame-K increased insulin secretion and augmented secretion induced by glucose. Sucralose increased biphasic increase in [Ca(2+)](c). The second sustained phase was blocked by removal of extracellular calcium and addition of nifedipine. An inhibitor of inositol(1, 4, 5)-trisphophate receptor, 2-aminoethoxydiphenyl borate, blocked both phases of [Ca(2+)](c) response. The effect of sucralose on [Ca(2+)](c) was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a G(q) inhibitor. Sucralose also induced sustained elevation of [cAMP](c), which was only partially inhibited by removal of extracellular calcium and nifedipine. Finally, mouse islets expressed T1R2 and T1R3, and artificial sweeteners stimulated insulin secretion.

Conclusions: Sweet taste receptor is expressed in beta-cells, and activation of this receptor induces insulin secretion by Ca(2+) and cAMP-dependent mechanisms.

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Effect of artificial sweeteners on insulin secretion in MIN6 cells.(A) MIN6 cells were incubated for 60 min with or without 50 mM saccharin, 50 mM sucralose or 50 mM acesulfame-K in the presence of 3 or 25 mM glucose, and insulin secretion was measured. Values are expressed as means±S.E. for four experiments. *: P<0.05 vs 3 mM glucose, **: P<0.05 vs 25 mM glucose. Note that 50 mM mannitol did not affect insulin secretion. (B) MIN6 cells were incubated for 60 min with 0, 1, 10 or 50 mM sucralose in the presence of 3 mM glucose, and insulin secretion was measured. Values are expressed as mean±S. E. for four experiments. *: P<0.05 vs 3 mM glucose alone. (C) MIN6 cells were incubated for 60 min with 3, 8.3 or 25 mM glucose in the presence (•) and absence (○) of 50 mM sucralose. Values are expressed as mean±S. E. for four experiments. *: P<0.05 vs without sucralose.
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pone-0005106-g002: Effect of artificial sweeteners on insulin secretion in MIN6 cells.(A) MIN6 cells were incubated for 60 min with or without 50 mM saccharin, 50 mM sucralose or 50 mM acesulfame-K in the presence of 3 or 25 mM glucose, and insulin secretion was measured. Values are expressed as means±S.E. for four experiments. *: P<0.05 vs 3 mM glucose, **: P<0.05 vs 25 mM glucose. Note that 50 mM mannitol did not affect insulin secretion. (B) MIN6 cells were incubated for 60 min with 0, 1, 10 or 50 mM sucralose in the presence of 3 mM glucose, and insulin secretion was measured. Values are expressed as mean±S. E. for four experiments. *: P<0.05 vs 3 mM glucose alone. (C) MIN6 cells were incubated for 60 min with 3, 8.3 or 25 mM glucose in the presence (•) and absence (○) of 50 mM sucralose. Values are expressed as mean±S. E. for four experiments. *: P<0.05 vs without sucralose.

Mentions: To determine the function of the sweet taste receptor expressed in MIN6 cells, we examined whether artificial sweeteners affected insulin secretion. As shown in Figure 2A, sucralose stimulated insulin secretion in the presence of a low concentration of glucose. Likewise, saccharin stimulated insulin secretion and acesulfame-K was much more potent. Note that 50 mM mannitol did not affect insulin secretion (data not shown). Saccharin and acesulfame-K also increased insulin secretion induced by a high concentration of glucose. Figure 2B depicts the dose-response relationship of the sucralose effect. The effect of sucralose was evident at a concentration of 50 mM. As shown in Figure 2C, sucralose augmented glucose-induced insulin secretion. Hence, agonists of the sweet taste receptor in the taste buds of the tongue were able to induce insulin secretion from MIN6 cells.


Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.

Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Kojima I - PLoS ONE (2009)

Effect of artificial sweeteners on insulin secretion in MIN6 cells.(A) MIN6 cells were incubated for 60 min with or without 50 mM saccharin, 50 mM sucralose or 50 mM acesulfame-K in the presence of 3 or 25 mM glucose, and insulin secretion was measured. Values are expressed as means±S.E. for four experiments. *: P<0.05 vs 3 mM glucose, **: P<0.05 vs 25 mM glucose. Note that 50 mM mannitol did not affect insulin secretion. (B) MIN6 cells were incubated for 60 min with 0, 1, 10 or 50 mM sucralose in the presence of 3 mM glucose, and insulin secretion was measured. Values are expressed as mean±S. E. for four experiments. *: P<0.05 vs 3 mM glucose alone. (C) MIN6 cells were incubated for 60 min with 3, 8.3 or 25 mM glucose in the presence (•) and absence (○) of 50 mM sucralose. Values are expressed as mean±S. E. for four experiments. *: P<0.05 vs without sucralose.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2663034&req=5

pone-0005106-g002: Effect of artificial sweeteners on insulin secretion in MIN6 cells.(A) MIN6 cells were incubated for 60 min with or without 50 mM saccharin, 50 mM sucralose or 50 mM acesulfame-K in the presence of 3 or 25 mM glucose, and insulin secretion was measured. Values are expressed as means±S.E. for four experiments. *: P<0.05 vs 3 mM glucose, **: P<0.05 vs 25 mM glucose. Note that 50 mM mannitol did not affect insulin secretion. (B) MIN6 cells were incubated for 60 min with 0, 1, 10 or 50 mM sucralose in the presence of 3 mM glucose, and insulin secretion was measured. Values are expressed as mean±S. E. for four experiments. *: P<0.05 vs 3 mM glucose alone. (C) MIN6 cells were incubated for 60 min with 3, 8.3 or 25 mM glucose in the presence (•) and absence (○) of 50 mM sucralose. Values are expressed as mean±S. E. for four experiments. *: P<0.05 vs without sucralose.
Mentions: To determine the function of the sweet taste receptor expressed in MIN6 cells, we examined whether artificial sweeteners affected insulin secretion. As shown in Figure 2A, sucralose stimulated insulin secretion in the presence of a low concentration of glucose. Likewise, saccharin stimulated insulin secretion and acesulfame-K was much more potent. Note that 50 mM mannitol did not affect insulin secretion (data not shown). Saccharin and acesulfame-K also increased insulin secretion induced by a high concentration of glucose. Figure 2B depicts the dose-response relationship of the sucralose effect. The effect of sucralose was evident at a concentration of 50 mM. As shown in Figure 2C, sucralose augmented glucose-induced insulin secretion. Hence, agonists of the sweet taste receptor in the taste buds of the tongue were able to induce insulin secretion from MIN6 cells.

Bottom Line: The effect of sucralose on [Ca(2+)](c) was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a G(q) inhibitor.Sucralose also induced sustained elevation of [cAMP](c), which was only partially inhibited by removal of extracellular calcium and nifedipine.Sweet taste receptor is expressed in beta-cells, and activation of this receptor induces insulin secretion by Ca(2+) and cAMP-dependent mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.

ABSTRACT

Background: Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets.

Methodology/principal findings: The expression of the sweet taste receptor was determined by RT-PCR and immunohistochemistry. Changes in cytoplasmic Ca(2+) ([Ca(2+)](c)) and cAMP ([cAMP](c)) were monitored in MIN6 cells using fura-2 and Epac1-camps. Activation of protein kinase C was monitored by measuring translocation of MARCKS-GFP. Insulin was measured by radioimmunoassay. mRNA for T1R2, T1R3, and gustducin was expressed in MIN6 cells. In these cells, artificial sweeteners such as sucralose, succharin, and acesulfame-K increased insulin secretion and augmented secretion induced by glucose. Sucralose increased biphasic increase in [Ca(2+)](c). The second sustained phase was blocked by removal of extracellular calcium and addition of nifedipine. An inhibitor of inositol(1, 4, 5)-trisphophate receptor, 2-aminoethoxydiphenyl borate, blocked both phases of [Ca(2+)](c) response. The effect of sucralose on [Ca(2+)](c) was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a G(q) inhibitor. Sucralose also induced sustained elevation of [cAMP](c), which was only partially inhibited by removal of extracellular calcium and nifedipine. Finally, mouse islets expressed T1R2 and T1R3, and artificial sweeteners stimulated insulin secretion.

Conclusions: Sweet taste receptor is expressed in beta-cells, and activation of this receptor induces insulin secretion by Ca(2+) and cAMP-dependent mechanisms.

Show MeSH
Related in: MedlinePlus