Sweet Taste Receptor Expressed in Pancreatic β-Cells Activates the Calcium and Cyclic AMP Signaling Systems and Stimulates Insulin Secretion

Nakagawa, Yuko; Nagasawa, Mitsuru; Yamada, Satoko; Hara, Akemi; Mogami, Hideo; Nikolaev, Viacheslav O.; Lohse, Martin J.; Shigemura, Noriatsu; Ninomiya, Yuzo; Kojima, Itaru

doi:10.1371/journal.pone.0005106

Cited by 273 publications

(316 citation statements)

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“…We hypothesize that in spermatids their activities converge on a common second messenger that controls spermatid differentiation and maturation. In taste cells, TAS1Rs are known to trigger Ca 2+ signaling pathways and affect cAMP levels (3,4,24). GNAT3 is closely related to the α-subunits of retinal transducins (GNAT1 and GNAT2) (53,56) that activate retinal (type 6) phosphodiesterases (PDEs) (53,56,57).…”

Section: Discussionmentioning

confidence: 99%

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Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility

Mosinger

Redding

Parker

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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TAS1R taste receptors and their associated heterotrimeric G protein gustducin are involved in sugar and amino acid sensing in taste cells and in the gastrointestinal tract. They are also strongly expressed in testis and sperm, but their functions in these tissues were previously unknown. Using mouse models, we show that the genetic absence of both TAS1R3, a component of sweet and amino acid taste receptors, and the gustducin α-subunit GNAT3 leads to malespecific sterility. To gain further insight into this effect, we generated a mouse model that expressed a humanized form of TAS1R3 susceptible to inhibition by the antilipid medication clofibrate. Sperm formation in animals without functional TAS1R3 and GNAT3 is compromised, with malformed and immotile sperm. Furthermore, clofibrate inhibition of humanized TAS1R3 in the genetic background of Tas1r3 −/− , Gnat3 −/− doubly null mice led to inducible male sterility. These results indicate a crucial role for these extraoral "taste" molecules in sperm development and maturation. We previously reported that blocking of human TAS1R3, but not mouse TAS1R3, can be achieved by common medications or chemicals in the environment. We hypothesize that even low levels of these compounds can lower sperm count and negatively affect human male fertility, which common mouse toxicology assays would not reveal. Conversely, we speculate that TAS1R3 and GNAT3 activators may help infertile men, particularly those that are affected by some of the mentioned inhibitors and/or are diagnosed with idiopathic infertility involving signaling pathway of these receptors.phenoxy compounds | spermiogenesis

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Section: Discussionmentioning

confidence: 99%

“…Although once thought to function only in taste buds, TAS1R receptors are also expressed in gut enteroendocrine cells and pancreatic islet cells, where they contribute to nutrient sensing and regulation of glucose metabolism (22)(23)(24)(25). Additional reports have shown their expression in brain, although their functional role there is unclear (26).…”

mentioning

confidence: 99%

Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility

Mosinger

Redding

Parker

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…corresponds to the circulating concentration of L-glutamate (i.e. between 100 and 300 lM) in blood (Nasset et al 1979;Serra et al 1991 (Fig. 2D).…”

Section: Expression Of Tas1r Family Members In Pancreatic Min6 B-cellsmentioning

confidence: 93%

Amino acid taste receptor regulates insulin secretion in pancreatic β-cell line MIN6 cells

et al. 2011

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Amino acids such as L-glutamate and L-arginine are potent stimuli for insulin secretion from pancreatic b-cells. However, the precise molecular mechanisms of amino acid-induced insulin secretion have only partly understood. In this study, we show here that mouse pancreatic b-cell line MIN6 cells expressed amino acid taste receptor (heterodimer of type 1 taste G protein-coupled receptor member 1 and member 3; Tas1R1 and Tas1R3, respectively). We found that administration of L-glutamate or L-arginine to MIN6 cells caused the increase in free intracellular concentrations of both inositol-1,4,5-triphosphate (IP 3 ) and Ca 2+ , and umami substance inocinate enhanced the effects of L-glutamate. Effects of amino acids on intracellular IP 3 and Ca 2+ concentration were diminished by application of lactisole, a Tas1R3 receptor antagonist. Furthermore, we investigated the effect of amino acids on the insulin release from MIN6 cells by both ELISA and total internal reflection fluorescence microscopy. Application of L-glutamate or L-arginine significantly increased the release of insulin, whereas inhibited by the application of lactisole. Based on these findings, we propose that heterodimer of Tas1R1 and Tas1R3 is the fundamental receptor for the sensing amino acids and regulates the amino acid-induced insulin secretion in pancreatic b-cells.

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“…Sweet taste receptors have now been found in different tissues such as the pancreas 11 , intestine 12,13 and recently rat and mouse brain 14 . These findings contributed to the formulation of our hypothesis that artificial sweeteners enhance detrusor muscle contraction via activation of the sweet taste receptors T1R2/T1R3 in the urinary bladder.…”

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confidence: 99%

Expression and Distribution of the Sweet Taste Receptor Isoforms T1R2 and T1R3 in Human and Rat Bladders

2011

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Purpose: Artificial sweeteners have been shown to augment bladder contraction. We hypothesised that artificial sweeteners activate sweet taste receptors in the bladder; therefore, we investigated the expression of sweet taste receptors in human and rat bladders.Materials and Methods: Sections of human and rat bladder were cut from paraffin blocks and stained by immunohistochemistry for expression of T1R2 and T1R3 sweet taste receptors. Bladder homogenates were subjected to SDS-polyacrylamide electrophoresis followed by immunoblotting for expression of T1R2 and T1R3 receptors. Strips of rat bladder, with and without the urothelium, were suspended in organ baths and the contractile response to 10Hz electrical field stimulation, in the absence and presence of saccharin 10 -8 M -10 -3 M, was obtained. Responses to KCl in the absence and presence of saccharin and saccharin plus zinc were determined.Results: T1R2 and T1R3 sweet taste receptors were expressed in the urothelium of human and rat bladder. Immunostaining was evident in the plasma membrane of the three cell types of the urothelium and in particular the umbrella cells. Immunoblotting revealed bands at expected molecular weights in both human and rat bladder homogenates. Saccharin augmented rat bladder smooth muscle contraction to electrical field stimulation only when the urothelium was present in the bladder strip.Zinc blocked the enhancing effect of saccharin on responses to KCl.Conclusion: T1R2 and T1R3 sweet taste receptors are expressed in the urothelium of human and rat bladder. Activation of these receptors by artificial sweeteners may result in augmentation of bladder contraction.3

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Sweet Taste Receptor Expressed in Pancreatic β-Cells Activates the Calcium and Cyclic AMP Signaling Systems and Stimulates Insulin Secretion

Cited by 273 publications

References 30 publications

Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility

Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility

Amino acid taste receptor regulates insulin secretion in pancreatic β-cell line MIN6 cells

Expression and Distribution of the Sweet Taste Receptor Isoforms T1R2 and T1R3 in Human and Rat Bladders

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