3 years ago

Endocytosis of KATP Channels Drives Glucose-Stimulated Excitation of Pancreatic β Cells

Endocytosis of KATP Channels Drives Glucose-Stimulated Excitation of Pancreatic β Cells
Jong Cheol Rah, Suk-Ho Lee, Hye-Hyun Kim, Jung Nyeo Chun, Won-Kyung Ho, Myong-Ho Jeong, Min Jeong Kwon, Young-Sun Ji, Jong-Sun Kang, Young-Eun Han, Sun-Hyun Park


Insulin secretion from pancreatic β cells in response to high glucose (HG) critically depends on the inhibition of KATP 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 KATP channel plays a major role. Upon HG stimulation, resting membrane potential depolarized by 30.6 mV (from −69.2 to −38.6 mV) and KATP 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 KATP 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 KATP channel surface density plays a greater role than ATP-dependent gating in regulating β cell excitability.

Publisher URL: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31873-9

DOI: 10.1016/j.celrep.2017.12.049

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