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From insulin synthesis to secretion: Alternative splicing of type 2 ryanodine receptor gene is essential for insulin secretion in pancreatic β cells.
- Source :
-
International Journal of Biochemistry & Cell Biology . Oct2017 Part B, Vol. 91, p176-183. 8p. - Publication Year :
- 2017
-
Abstract
- Increases in the intracellular Ca 2+ concentration in pancreatic islets, resulting from the Ca 2+ mobilization from the intracellular source through the ryanodine receptor, are essential for insulin secretion by glucose. Cyclic ADP-ribose, a potent Ca 2+ 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 Ca 2+ 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 Ca 2+ release. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13572725
- Volume :
- 91
- Database :
- Academic Search Index
- Journal :
- International Journal of Biochemistry & Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 126871398
- Full Text :
- https://doi.org/10.1016/j.biocel.2017.07.009