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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ross, C. A. Depaoli, A. M. Swift, H. Moody, M. M. Sharp, A. H. Blondel, O. Bell, G. I. |
| Description | Author Affiliation: Blondel O ( Howard Hughes Medical Institute, University of Chicago, IL 60637.); |
| Abstract | Calcium ions play a central role in stimulus-secretion coupling in pancreatic beta cells, and an elevation of cytosolic Ca2+ levels is necessary for insulin secretion. Inositol 1,4,5-trisphosphate mobilizes intracellular Ca2+ stores in the beta cell by binding to specific receptors that are ligand-activated Ca2+ channels. The inositol trisphosphate receptors comprise a family of structurally related proteins with distinct but overlapping tissue distributions. Previous studies indicated that the predominant inositol trisphosphate receptor subtype expressed in rat pancreatic islets was the protein designated IP3R-3. We have confirmed the expression of IP3R-3 in pancreatic islets by immunohistocytochemistry and localized this protein to the secretory granules of insulin-secreting beta cells and somatostatin-secreting delta cells by immunogold electron microscopy. Secretory granules contain high levels of Ca2+, and the presence of IP3R-3 in the granule provides a mechanism for mobilizing granule Ca2+ stores in response to glucose and/or hormones. The release of Ca2+ from granule stores would increase the Ca2+ concentration in the surrounding cytoplasm and promote rapid exocytosis of granules, especially those granules in close proximity to the plasma membrane. The levels of IP3R-3 were increased in pancreatic islets of diabetic rats and rats that had been refed after a period of fasting. They were also increased in rat insulinoma RINm5F cells cultured in 25 mM glucose compared with cells cultured in 5 mM glucose. The localization of IP3R-3 to secretory granules of insulin-secreting beta cells and somatostatin-secreting delta cells suggests that granule Ca2+ stores actively participate in the secretory process and that their release is regulated by inositol 1,4,5-trisphosphate. The regulation of IP3R-3 levels by glucose, diabetes, and refeeding may allow the beta cell to adjust the insulin secretory response to changing physiological conditions. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 16 |
| Volume Number | 91 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1994-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Calcium Channels Biosynthesis Cytoplasmic Granules Metabolism Gene Expression Regulation Inositol 1,4,5-Trisphosphate Islets Of Langerhans Receptors, Cytoplasmic And Nuclear Amino Acid Sequence Animals Isolation & Purification Cell Compartmentation Cells, Cultured Inositol 1,4,5-Trisphosphate Receptors Insulin Secretion Insulinoma Pathology Molecular Sequence Data Somatostatin Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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