AI Article Synopsis
- * When β cells are stimulated by HG, there is a significant depolarization of the resting membrane potential and a drastic decrease in K conductance, while intracellular ATP increases only moderately.
- * Blocking endocytosis with inhibitors prevented the reduction of K channel density on the cell surface and the associated depolarization, indicating that K channel surface density is crucial for regulating β cell activity rather than solely ATP levels.
Article Abstract
Insulin secretion from pancreatic β cells in response to high glucose (HG) critically depends on the inhibition of K channel activity in HG. It is generally believed that HG-induced effects are mediated by the increase in intracellular ATP, but here, we showed that, in INS-1 cells, endocytosis of K channel plays a major role. Upon HG stimulation, resting membrane potential depolarized by 30.6 mV (from -69.2 to -38.6 mV) and K conductance decreased by 91% (from 0.243 to 0.022 nS/pF), whereas intracellular ATP was increased by only 47%. HG stimulation induced internalization of K channels, causing a significant decrease in surface channel density, and this decrease was completely abolished by inhibiting endocytosis using dynasore, a dynamin inhibitor, or a PKC inhibitor. These drugs profoundly inhibited HG-induced depolarization. Our results suggest that the control of K channel surface density plays a greater role than ATP-dependent gating in regulating β cell excitability.
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| http://dx.doi.org/10.1016/j.celrep.2017.12.049 | DOI Listing |
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