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Ca 2 +-induced Ca 2...
Ca 2 +-induced Ca 2 + Release via Inositol 1,4,5-trisphosphate Receptors Is Amplified by Protein Kinase A and Triggers Exocytosis in Pancreatic β-Cells
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Dyachok, Oleg (author)
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Gylfe, Erik (author)
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(publisher)
- 2004
- 2004
- English.
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In: Journal of Biological Chemistry. - 0021-9258. ; 279:44, 45455-45461
Abstract
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- Hormones, such as glucagon and glucagon-like peptide-1, potently amplify nutrient stimulated insulin secretion by raising cAMP. We have studied how cAMP affects Ca 2+ -induced Ca 2+ release (CICR) in pancreatic β-cells from mice and rats and the role of CICR in secretion. CICR was observed as pronounced Ca 2+ spikes on top of glucose- or depolarization-dependent rise of the cytoplasmic Ca 2+ concentration ([Ca 2+ ] i ). cAMP-elevating agents strongly promoted CICR. This effect involved sensitization of the receptors underlying CICR, because many cells exhibited the characteristic Ca 2+ spiking at low or even in the absence of depolarization-dependent elevation of [Ca 2+ ] i . The cAMP effect was mimicked by a specific activator of protein kinase A in cells unresponsive to activators of cAMP-regulated guanine nucleotide exchange factor. Ryanodine pretreatment, which abolishes CICR mediated by ryanodine receptors, did not prevent CICR. Moreover, a high concentration of caffeine, known to activate ryanodine receptors independently of Ca 2+ , failed to mobilize intracellular Ca 2+ . On the contrary, a high caffeine concentration abolished CICR by interfering with inositol 1,4,5-trisphosphate receptors (IP 3 Rs). Therefore, the cell-permeable IP 3 R antagonist 2-aminoethoxydiphenyl borate blocked the cAMP-promoted CICR. Individual CICR events in pancreatic β-cells were followed by [Ca 2+ ] i spikes in neighboring human erythroleukemia cells, used to report secretory events in the β-cells. The results indicate that protein kinase A-mediated promotion of CICR via IP 3 Rs is part of the mechanism by which cAMP amplifies insulin release.
Subject headings
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Cell and Molecular Biology (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska grundvetenskaper (hsv)
- Cell- och molekylärbiologi (hsv)
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Physiology (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska grundvetenskaper (hsv)
- Fysiologi (hsv)
- Medical and Health Sciences (hsv)
- Clinical Medicine (hsv)
- Endocrinology and Diabetes (hsv)
- Medicin och hälsovetenskap (hsv)
- Klinisk medicin (hsv)
- Endokrinologi och diabetes (hsv)
- MEDICINE (svep)
- Morphology, cell biology, pathology (svep)
- Cell biology (svep)
- MEDICIN (svep)
- Morfologi, cellbiologi, patologi (svep)
- Cellbiologi (svep)
- MEDICINE (svep)
- Physiology and pharmacology (svep)
- Physiology (svep)
- MEDICIN (svep)
- Fysiologi och farmakologi (svep)
- Fysiologi (svep)
- MEDICINE (svep)
- Dermatology and venerology,clinical genetics, internal medicine (svep)
- Internal medicine (svep)
- Diabetology (svep)
- MEDICIN (svep)
- Dermatologi och venerologi, klinisk genetik, invärtesmedicin (svep)
- Invärtesmedicin (svep)
- Diabetologi (svep)
- medicinsk cellbiologi (uu)
- Medical Cell Biology (uu)
Keyword
- Animals
- Calcium/*metabolism
- Calcium Channels/*physiology
- Cells; Cultured
- Cyclic AMP/physiology
- Cyclic AMP-Dependent Protein Kinases/*physiology
- Exocytosis
- Glucagon/pharmacology
- Glucagon-Like Peptide 1
- Islets of Langerhans/*metabolism
- Mice
- Mice; Obese
- Peptide Fragments/pharmacology
- Protein Precursors/pharmacology
- Rats
- Rats; Wistar
- Receptors; Cytoplasmic and Nuclear/*physiology
- Research Support; Non-U.S. Gov't
- Ryanodine/pharmacology
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