| Extracellular Calcium influx activates Adenylate Cyclase 1 and potentiates Insulin secretion in MIN6 cells. | |
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MedLine Citation:
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PMID: 23282092 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Intracellular cAMP and Ca2+ 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 this study, we investigated the interplay between intracellular cAMP and Ca2+ concentrations ([cAMP]i and [Ca2+]i, respectively) in the pancreatic β cell line MIN6 cells using total internal reflection fluorescence microscopy. For measuring [cAMP]i, we developed a genetically encoded yellow fluorescent biosensor for cAMP (fluorescent cAMP indicator; Flamindo), 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 Ca2+ channel agonist or ionomycin to induce extracellular Ca2+ influx evoked the elevation of [cAMP]i, whereas application of carbachol or thapsigargin, which mobilize Ca2+ from internal stores, did not evoke the elevation of [cAMP]i. We performed RT-PCR analysis and found that Ca2+-sensitive adenylate cyclase 1 (Adcy1) 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 [Ca2+]i. Taken together, these findings demonstrate that Adcy1 plays an important role in the control of pancreatic β cell cAMP homeostasis and insulin secretion. |
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Authors:
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Tetsuya Kitaguchi; Manami Oya; Yoshiko Wada; Takashi Tsuboi; Atsushi Miyawaki |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-3 |
Journal Detail:
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Title: The Biochemical journal Volume: - ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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