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- Eberhardson, Michael
(författare)
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The interplay of ions in the stimulation of the pancreatic -cell
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glucose stimulation of insulin release is mediated by depolarisation of the pancreatic β-cells with accompanying entry of Ca2+ through voltage-dependent channels. An important feature of the glucose-induced depolarisation is its rhythmicity causing oscillations of the cytoplasmic Ca2+ concentration ([Ca2+]i), which trigger pulsatile release of insulin. In addition to inducing slow [Ca2+]i oscillations (0.2-0.5/min), glucose is known to be a cofactor for brief transients of 10-20 sec duration due to intracellular mobilisation of Ca2+. In the present study microfluorometric technique was used for elucidating how various ion permeabilities interact in the generation of Ca2+ signals in individual β-cells. Increased Ca2+ entry or inhibition of K+ channels promoted the glucose-induced slow oscillations of [Ca2+]i. Studying how inhibition of K+ channels contributed to the generation of slow oscillations, it was discovered that tetraehylammonium+, quinine, and Cs+ precipitated pronounced Ca2+ transients in β-cells stimulated with glucose or tolbutamide. Similar transients were obtained when the entry of Na+ was stimulated with the Na+ channel agonist veratridine. The transients differed from those previously described in reflecting voltage-dependent entry of Ca2+ instead of mobilisation of intracellular Ca2+ stores. The steady-state concentration of Cl- in unstimulated β-cells was found to be 34 mM, indicating that Cl- is accumulated against its electrochemical gradient. Further studies showed that glucose increases the Cl- permeability, an effect which is supposed to contribute to the depolarising action of the sugar. Evidence was provided that transmembrane Cl- fluxes are important for the generation of the slow oscillations as well as for the fast transients of [Ca2+]i, which both depend on entry of Ca2+ through voltage-dependent channels.
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