論文 - 詳細
| RRC ID | 49260 |
|---|---|
| 著者 | Kitaguchi T, Oya M, Wada Y, Tsuboi T, Miyawaki A. |
| タイトル | Extracellular calcium influx activates adenylate cyclase 1 and potentiates insulin secretion in MIN6 cells. |
| ジャーナル | Biochem J |
| Abstract |
Intracellular cAMP and Ca(2+) are important second messengers that regulate insulin secretion in pancreatic β-cells; however, the molecular mechanism underlying their mutual interaction for exocytosis is not fully understood. In the present study, we investigated the interplay between intracellular cAMP and Ca(2+) concentrations ([cAMP](i) and [Ca(2+)](i) respectively) in the pancreatic β-cell line MIN6 using total internal reflection fluorescence microscopy. For measuring [cAMP](i), we developed a genetically encoded yellow fluorescent biosensor for cAMP [Flamindo (fluorescent cAMP indicator)], which changes fluorescence intensity with cAMP binding. Application of high-KCl or glucose to MIN6 cells induced the elevation of [cAMP](i) and exocytosis. Furthermore, application of an L-type Ca(2+) channel agonist or ionomycin to induce extracellular Ca(2+) influx evoked the elevation of [cAMP](i), whereas application of carbachol or thapsigargin, which mobilize Ca(2+) from internal stores, did not evoke the elevation of [cAMP](i). We performed RT (reverse transcription)-PCR analysis and found that Ca(2+)-sensitive Adcy1 (adenylate cyclase 1) was expressed in MIN6 cells. Knockdown of endogenous ADCY1 by small interference RNA significantly suppressed glucose-induced exocytosis and the elevation of both [cAMP](i) and [Ca(2+)](i). Taken together, the findings of the present study demonstrate that ADCY1 plays an important role in the control of pancreatic β-cell cAMP homoeostasis and insulin secretion. |
| 巻・号 | 450(2) |
| ページ | 365-73 |
| 公開日 | 2013-3-1 |
| DOI | 10.1042/BJ20121022 |
| PII | BJ20121022 |
| PMID | 23282092 |
| MeSH | Adenylyl Cyclases / genetics Adenylyl Cyclases / metabolism* Animals COS Cells Calcium / metabolism* Calcium Signaling Cells, Cultured Chlorocebus aethiops Cyclic AMP / metabolism Glucose / metabolism Insulin / metabolism* Insulin Secretion Mice Transfection |
| IF | 4.097 |
| 引用数 | 43 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 14 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | Flamindo/pcDNA3 (RDB15247) Flamindo (R279E)/pcDNA3 (RDB15248). |