Article ; Online: Activation of the Na+/K+-ATPase by insulin and glucose as a putative negative feedback mechanism in pancreatic beta-cells.
Pflugers Archiv : European journal of physiology
2008 Volume 457, Issue 6, Page(s) 1351–1360
Abstract: ... hyper-polarised V (m). Inhibiting insulin signalling in SUR1(-/-) beta-cells blunted the glucose-induced ... K(+)-ATPase presumably by increasing [ATP](c). Insulin can also stimulate the pump and potentiate ... current. Elevating glucose in SUR1(-/-) beta-cells resulted in a transient fall in V (m) and [Ca(2+)](c ...
Abstract | Pancreatic beta-cells of sulfonylurea receptor type 1 knock-out (SUR1(-/-)) mice exhibit an oscillating membrane potential (V (m)) demonstrating that hyper-polarisation occurs despite the lack of K(ATP) channels. We hypothesize that glucose activates the Na(+)/K(+)-ATPase thus increasing a hyper-polarising current. Elevating glucose in SUR1(-/-) beta-cells resulted in a transient fall in V (m) and [Ca(2+)](c) independent of sarcoplasmic and endoplasmic reticulum Ca(2+)-activated ATPase (SERCA) activation. This was not affected by K(+) channel blockade but inhibited by ATP depletion and by ouabain. Increasing glucose also reduced [Na(+)](c), an effect reversed by ouabain. Exogenously applied insulin decreased [Na(+)](c) and hyper-polarised V (m). Inhibiting insulin signalling in SUR1(-/-) beta-cells blunted the glucose-induced decrease of [Ca(2+)](c). Tolbutamide (1 mmol/l) disclosed the SERCA-independent effect of glucose on [Ca(2+)](c) in wild-type beta-cells. The data show that in SUR1(-/-) beta-cells, glucose activates the Na(+)/K(+)-ATPase presumably by increasing [ATP](c). Insulin can also stimulate the pump and potentiate the effect of glucose. Pathways involving the pump may thus serve as potential drug targets in certain metabolic disorders. |
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MeSH term(s) | Adenosine Triphosphate/physiology ; Animals ; Calcium/metabolism ; Enzyme Activation ; Glucose/pharmacology ; Insulin/pharmacology ; Insulin/physiology ; Insulin-Secreting Cells/metabolism ; Membrane Potentials/drug effects ; Membrane Potentials/physiology ; Mice ; Signal Transduction ; Sodium-Potassium-Exchanging ATPase/drug effects ; Sodium-Potassium-Exchanging ATPase/metabolism | |||||
Chemical Substances | Insulin ; Adenosine Triphosphate (8L70Q75FXE) ; Sodium-Potassium-Exchanging ATPase (EC 3.6.3.9) ; Glucose (IY9XDZ35W2) ; Calcium (SY7Q814VUP) | |||||
Language | English | |||||
Publishing date | 2008-10-03 | |||||
Publishing country | Germany | |||||
Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | |||||
ZDB-ID | 6380-0 | |||||
ISSN | 1432-2013 ; 0031-6768 | |||||
ISSN (online) | 1432-2013 | |||||
ISSN | 0031-6768 | |||||
DOI | 10.1007/s00424-008-0592-4 | |||||
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Database | MEDical Literature Analysis and Retrieval System OnLINE |
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