TY - JOUR
T1 - From insulin synthesis to secretion
T2 - Alternative splicing of type 2 ryanodine receptor gene is essential for insulin secretion in pancreatic β cells
AU - Okamoto, Hiroshi
AU - Takasawa, Shin
AU - Yamamoto, Yasuhiko
N1 - Funding Information:
The authors are grateful to Mr. Brent Bell for critical reading of the manuscript. We are also grateful to Dr. Michio Kuroki, Yamagata City Hospital SAISEIKAN, Dr. Koji Nata, Department of Medical Biochemistry, Iwate Medical University, School of Pharmacy, and Dr. Takayuki Ikeda, Department of Biochemistry, Kanazawa Medical University for technical assistance and discussions. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan , and Japan Science and Technology Agency .
Funding Information:
The authors are grateful to Mr. Brent Bell for critical reading of the manuscript. We are also grateful to Dr. Michio Kuroki, Yamagata City Hospital SAISEIKAN, Dr. Koji Nata, Department of Medical Biochemistry, Iwate Medical University, School of Pharmacy, and Dr. Takayuki Ikeda, Department of Biochemistry, Kanazawa Medical University for technical assistance and discussions. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and Japan Science and Technology Agency.
Publisher Copyright:
© 2017
PY - 2017/10
Y1 - 2017/10
N2 - Increases in the intracellular Ca2+ concentration in pancreatic islets, resulting from the Ca2+ mobilization from the intracellular source through the ryanodine receptor, are essential for insulin secretion by glucose. Cyclic ADP-ribose, a potent Ca2+ mobilizing second messenger synthesized from NAD+ by CD38, regulates the opening of ryanodine receptor. A novel ryanodine receptor mRNA (the islet-type ryanodine receptor) was found to be generated from the type 2 ryanodine receptor gene by the alternative splicing of exons 4 and 75. The islet-type ryanodine receptor mRNA is expressed in a variety of tissues such as pancreatic islets, cerebrum, cerebellum, and other neuro-endocrine cells, whereas the authentic type 2 ryanodine receptor mRNA (the heart-type ryanodine receptor) was found to be generated using GG/AG splicing of intron 75 and is expressed in the heart and the blood vessel. The islet-type ryanodine receptor caused a greater increase in the Ca2+ release by caffeine when expressed in HEK293 cells pre-treated with cyclic ADP-ribose, suggesting that the novel ryanodine receptor is an intracellular target for the CD38-cyclic ADP-ribose signal system in mammalian cells and that the tissue-specific alternative splicing of type 2 ryanodine receptor mRNA plays an important role in the functioning of the cyclic ADP-ribose-sensitive Ca2+ release.
AB - Increases in the intracellular Ca2+ concentration in pancreatic islets, resulting from the Ca2+ mobilization from the intracellular source through the ryanodine receptor, are essential for insulin secretion by glucose. Cyclic ADP-ribose, a potent Ca2+ mobilizing second messenger synthesized from NAD+ by CD38, regulates the opening of ryanodine receptor. A novel ryanodine receptor mRNA (the islet-type ryanodine receptor) was found to be generated from the type 2 ryanodine receptor gene by the alternative splicing of exons 4 and 75. The islet-type ryanodine receptor mRNA is expressed in a variety of tissues such as pancreatic islets, cerebrum, cerebellum, and other neuro-endocrine cells, whereas the authentic type 2 ryanodine receptor mRNA (the heart-type ryanodine receptor) was found to be generated using GG/AG splicing of intron 75 and is expressed in the heart and the blood vessel. The islet-type ryanodine receptor caused a greater increase in the Ca2+ release by caffeine when expressed in HEK293 cells pre-treated with cyclic ADP-ribose, suggesting that the novel ryanodine receptor is an intracellular target for the CD38-cyclic ADP-ribose signal system in mammalian cells and that the tissue-specific alternative splicing of type 2 ryanodine receptor mRNA plays an important role in the functioning of the cyclic ADP-ribose-sensitive Ca2+ release.
KW - Alternative splicing
KW - Cyclic ADP-ribose
KW - Poly(ADP-ribose) polymerase/synthetase
KW - Ryanodine receptor
KW - The OKAMOTO model
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U2 - 10.1016/j.biocel.2017.07.009
DO - 10.1016/j.biocel.2017.07.009
M3 - Review article
C2 - 28736243
AN - SCOPUS:85027413177
SN - 1357-2725
VL - 91
SP - 176
EP - 183
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
ER -