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Rapid turnover of p...
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Thore, SophiaUppsala universitet,Institutionen för medicinsk cellbiologi
(author)
Rapid turnover of phosphatidylinositol-4,5-bisphosphate in insulin-secreting cells mediated by Ca2+ and the ATP-to-ADP ratio
- Article/chapterEnglish2007
Publisher, publication year, extent ...
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American Diabetes Association,2007
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-12845
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-12845URI
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https://doi.org/10.2337/db06-0843DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Phosphatidylinositol-4,5-bisphosphate (PIP2) is important for a variety of cellular processes as a precursor for second messengers and by regulating ion channels, the cytoskeleton, and vesicle traffic in many types of cells, including insulin-secreting β-cells. Here, we applied evanescent wave microscopy and the PIP2-binding pleckstrin homology domain from phospholipase C (PLC)-δ fused to the green fluorescent protein to characterize the regulation of plasma membrane PIP2 in individual insulin-secreting MIN6 β-cells. Elevation of the glucose concentration from 3 to 11 mmol/l evoked antisynchronous oscillations of [PIP2] and cytoplasmic Ca2+concentration, consistent with PLC being periodically activated by the voltage-dependent Ca2+ influx. The effect of adenine nucleotides on [PIP2] was studied in cells permeabilized with α-toxin. ATP dose- dependently stimulated PIP2 synthesis with half-maximal effect at 300 μmol/l. Omission of the nucleotide resulted in rapid loss of PIP2 with t1/2 < 40 s. ADP also stimulated PIP2 formation, but this effect reflected local ATP formation and was prevented by the adenylate kinase inhibitor diadenosine-pentaphosphate. The ATP-induced PIP2 synthesis was counteracted by the ADP analog adenosine-5′-O-2-thiodiphosphate. We conclude that plasma membrane PIP2 is dynamically regulated by intracellular Ca2+ and the ATP-to-ADP ratio in insulin-secreting cells. The rapid turnover allows maintenance of PIP2 levels while generating second messengers of critical importance for insulin secretion.
Subject headings and genre
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Adenosine Diphosphate/*metabolism
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Adenosine Triphosphate/*metabolism
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Animals
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Calcium/*metabolism
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Cell Line
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Cell Membrane/metabolism
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Glucose
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Hydrolysis
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Insulin-Secreting Cells/*metabolism
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Mice
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Phosphatidylinositol 4;5-Diphosphate/*metabolism
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MEDICINE
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MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
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Wuttke, AnneUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)annwu514
(author)
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Tengholm, AndersUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)andeteng
(author)
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Uppsala universitetInstitutionen för medicinsk cellbiologi
(creator_code:org_t)
Related titles
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In:Diabetes: American Diabetes Association56:3, s. 818-8260012-17971939-327X
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