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- Gromada, J, et al.
(författare)
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Nateglinide, but not repaglinide, stimulates growth hormone release in rat pituitary cells by inhibition of K+ channels and stimulation of cyclic AMP-dependent exocytosis
- 2002
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 147:1, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- Objective: GH causes insulin resistance, impairs glycemic control and increases the risk of vascular diabetic complications. Sulphonylureas stimulate GH secretion and this study was undertaken to investigate the possible stimulatory effect of repaglinide and nateglinide, two novel oral glucose regulators, on critical steps of the stimulus-secretion coupling in single rat somatotrophs. Methods: Patch-clamp techniques were used to record whole-cell ATP-sensitive K+ (K-ATP) and delayed outward K+ currents, membrane potential and Ca2+-dependent exocytosis. GH release was measured from perifused rat somatotrophs. Results: Both nateglinide and repaglinide dose-dependently suppressed K-ATP channel activity with half-maximal inhibition being observed at 413 nM and 13 nM respectively. Both compounds induced action potential firing in the somatotrophs irrespective of whether GH-releasing hormone was present or not. The stimulation of electrical activity by nateglinide, but not repaglinide, was associated with an increased mean duration of the action potentials. The latter effect correlated with a reduction of the delayed outward K+ current, which accounts for action potential repolarization. The latter effect had a K-d of 19 muM but was limited to 38% inhibition. When applied at concentrations similar to those required to block K-ATP channels, nateglinide in addition potentiated Ca2+-evoked exocytosis 3.3-fold (K-d = 3 muM) and stimulated GH release 4.5-fold. The latter effect was not shared by repaglinide. The stimulation of exocytosis by nateglinide was mimicked by cAMP and antagonized by the protein kinase A inhibitor Rp-cAMPS. Conclusion: Nateglinide stimulates GH release by inhibition of plasma membrane K+ channels, elevation of cytoplasmic cAMP levels and stimulation of Ca2+-dependent exocytosis. By contrast, the effect of repaglinide was confined to inhibition of the K-ATP channels.
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- Rosén, Christian, et al.
(författare)
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Introducing biological phosphorus removal in an alternating plant by means of control: a full scale study
- 2006
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Ingår i: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 53:4-5, s. 133-141
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, a control strategy for introducing enhanced biological phosphorus removal (EBPR) in an alternating plant designed for enhanced biological nitrogen removal (EBNR) is presented. Alternating aerobic and anaerobic conditions to promote EBPR are provided by controlling the phases of the operational cycle, instead of a separate anaerobic volume. By utilising the control schemes already built in the STAR((R)) control system for nitrogen removal, the control strategy is fully integrated in the system. The control system relies on on-line measurements of nitrogen (ammonia and/or nitrate) and orthophosphate. The control strategy has been implemented in full-scale operation at the Avedore wastewater treatment plant in Denmark and the results show clear indications of success. The control strategy has operated robustly for several months with a 60% decrease in use of precipitation chemicals.
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