TY - JOUR
T1 - Effects of insulin signaling on mouse taste cell proliferation
AU - Takai, Shingo
AU - Watanabe, Yu
AU - Sanematsu, Keisuke
AU - Yoshida, Ryusuke
AU - Margolskee, Robert F.
AU - Jiang, Peihua
AU - Atsuta, Ikiru
AU - Koyano, Kiyoshi
AU - Ninomiya, Yuzo
AU - Shigemura, Noriatsu
N1 - Funding Information:
This work was supported by KAKENHI 17K17938 (S.T.), 15H02571 (Y.N.), and 15K11044 (N.S.) from the Scientific Research and Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers (S2605) from the Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. Wenwen Ren for advice on culturing taste bud organoids, Dr. Hans Clevers for providing the Wnt3a-producing cell line, Dr. Jeffery Whitsett for the R-spondin-producing cell lines, and Dr. Yuchio Yanagawa for providing GAD67-GFP mice. Ms. Patricia J. Watson helped us about English writing and editing. We appreciate technical assistance from the Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences.
Publisher Copyright:
© 2019 Takai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Expression of insulin and its receptor (IR) in rodent taste cells has been proposed, but exactly which types of taste cells express IR and the function of insulin signaling in taste organ have yet to be determined. In this study, we analyzed expression of IR mRNA and protein in mouse taste bud cells in vivo and explored its function ex vivo in organoids, using RT-PCR, immunohistochemistry, and quantitative PCR. In mouse taste tissue, IR was expressed broadly in taste buds, including in type II and III taste cells. With using 3-D taste bud organoids, we found insulin in the culture medium significantly decreased the number of taste cell and mRNA expression levels of many taste cell genes, including nucleoside triphosphate diphosphohydrolase-2 (NTPDase2), Tas1R3 (T1R3), gustducin, carbonic anhydrase 4 (CA4), glucose transporter-8 (GLUT8), and sodium-glucose cotransporter-1 (SGLT1) in a concentration-dependent manner. Rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR) signaling, diminished insulin’s effects and increase taste cell generation. Altogether, circulating insulin might be an important regulator of taste cell growth and/or proliferation via activation of the mTOR pathway.
AB - Expression of insulin and its receptor (IR) in rodent taste cells has been proposed, but exactly which types of taste cells express IR and the function of insulin signaling in taste organ have yet to be determined. In this study, we analyzed expression of IR mRNA and protein in mouse taste bud cells in vivo and explored its function ex vivo in organoids, using RT-PCR, immunohistochemistry, and quantitative PCR. In mouse taste tissue, IR was expressed broadly in taste buds, including in type II and III taste cells. With using 3-D taste bud organoids, we found insulin in the culture medium significantly decreased the number of taste cell and mRNA expression levels of many taste cell genes, including nucleoside triphosphate diphosphohydrolase-2 (NTPDase2), Tas1R3 (T1R3), gustducin, carbonic anhydrase 4 (CA4), glucose transporter-8 (GLUT8), and sodium-glucose cotransporter-1 (SGLT1) in a concentration-dependent manner. Rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR) signaling, diminished insulin’s effects and increase taste cell generation. Altogether, circulating insulin might be an important regulator of taste cell growth and/or proliferation via activation of the mTOR pathway.
UR - http://www.scopus.com/inward/record.url?scp=85074876297&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074876297&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0225190
DO - 10.1371/journal.pone.0225190
M3 - Article
C2 - 31714935
AN - SCOPUS:85074876297
SN - 1932-6203
VL - 14
JO - PLoS One
JF - PLoS One
IS - 11
M1 - e0225190
ER -