A Novel Mechanism for the Suppression of a Voltage-gated Potassium Channel by Glucose-dependent Insulinotropic Polypeptide

The mechanisms involved in glucose regulation of insulin secretion by ATP-sensitive (KATP) and calcium-activated (KCA) potassium channels have been extensively studied, but less is known about the role of voltage-gated (KV) potassium channels in pancreatic β-cells. The incretin hormone, glucose-dependent insulinotropic polypeptide (GIP) stimulates insulin secretion by potentiating events underlying membrane depolarization and exerting direct effects on exocytosis. In the present study, we identified a novel role for GIP in regulating KV1.4 channel endocytosis. In GIP receptor-expressing HEK293 cells, GIP reduced A-type peak ionic of KV1.4 of of KV1.4 in a and on KV1.4 GIP of of KV1.4 in GIP in in A-type potassium peak in HEK293 in of a in reduced insulin KV1.4 insulin in novel role for GIP in regulating KV1.4 and of A-type potassium is for insulinotropic The mechanisms involved in glucose regulation of insulin secretion by ATP-sensitive (KATP) and calcium-activated (KCA) potassium channels have been extensively studied, but less is known about the role of voltage-gated (KV) potassium channels in pancreatic β-cells. The incretin hormone, glucose-dependent insulinotropic polypeptide (GIP) stimulates insulin secretion by potentiating events underlying membrane depolarization and exerting direct effects on exocytosis. In the present study, we identified a novel role for GIP in regulating KV1.4 channel endocytosis. In GIP receptor-expressing HEK293 cells, GIP reduced A-type peak ionic of KV1.4 of of KV1.4 in a and on KV1.4 GIP of of KV1.4 in GIP in in A-type potassium peak in HEK293 in of a in reduced insulin KV1.4 insulin in novel role for GIP in regulating KV1.4 and of A-type potassium is for insulinotropic insulinotropic polypeptide (GIP) glucose-dependent insulinotropic GIP ATP-sensitive calcium-activated voltage-gated glucose-dependent insulinotropic GIP ATP-sensitive calcium-activated voltage-gated and the involved in the of insulin secretion a insulin secretion is of ATP-sensitive (KATP) channels in membrane of and in by membrane by (KV) and (KCA) channels by potentiating the events underlying membrane depolarization in exerting direct effects on exocytosis. events incretin and of In the of of the and of and is known the of on membrane of the potassium channels the of channels of and involved in of of of in of channels the pancreatic the of and insulin have been and in and of potassium on the of and A-type by is by and and A-type is by KV1.4 of present in pancreatic of the have on the The on a role for GIP in the regulation of a of the and of channel potassium involved in the regulation of insulin cells, we GIP peak of KV1.4 a In KV1.4 in pancreatic and GIP A-type potassium in GIP and of KV1.4 and in of a in reduced insulin insulin the of for a role for of of the channel in the of insulin of a in and and pancreatic GIP of the for the and by and by of KV1.4 and in the and by and for the the a of in the of the KV1.4 the of a the The and the and in by and the by for and the by in and the a and reduced KV1.4 In in a of of and the of of and a of of the of of of KV1.4 for by the the on and the for of on a and of the KV1.4 and by and the of and the The of the of and on in in and ionic we a the The the and and and a of HEK293 for a of a for KV1.4 a the GIP for of and and for The and by and by and and of the and by of and for GIP and and a and a in and in in for in of and a for a for KV1.4 and The KV1.4 and insulin and and and a the by in glucose and a of the of for the the GIP and for in and glucose the a the of in the the and of a in the of KV1.4 in HEK293 in the of KV1.4 by GIP HEK293 a of the The KV1.4 in of in a in peak and by and The in peak in HEK293 cells, the in the of GIP The of GIP a of KV1.4 GIP the of in GIP the of GIP GIP the of GIP is by in the of in and in the of KV1.4 involved in the of KV1.4 peak by GIP The in KV1.4 peak of and is a GIP involved in the regulation of insulin of GIP in of GIP GIP of of in KV1.4 peak and of The and and the of KV1.4 peak the the of GIP on KV1.4 peak is involved in the regulation of in and is involved in the in KV1.4 ionic of GIP and of for the of GIP in the of a GIP of GIP on and of for the of GIP in the of GIP in the of and GIP and the and of a the in the of KV1.4 and in KV1.4 KV1.4 the of and in of KV1.4 the of and for and of KV1.4 the of for the of the of KV1.4 involved in GIP in KV1.4 the in the The been of of the channel GIP the peak by the the GIP the in KV1.4 is for of the of the of KV1.4 involved in regulating and The is for and membrane of the channel and the is the for and we a in the of of KV1.4 is in on the of for of the and and in of the by GIP peak and but The in the membrane of KV1.4 by is the in peak and of in the is a in in the of KV1.4 and in ionic and in of KV1.4 by of KV1.4 for the of in of in the of and The by in and by The and of the KV1.4 and the for and of and GIP and peak and In the of of and of GIP and the in of KV1.4 by of KV1.4 for in of in the of in and the for and the and of and and peak and the of of and the of GIP and the the and the in KV1.4 of channels been in in is in and in peak involved in and in KV1.4 peak by endocytosis. the of KV1.4 GIP The on is the is of KV1.4 channels in the a channel is in membrane of KV1.4 GIP and of KV1.4 channels present in the membrane reduced by GIP in KV1.4 peak by on GIP in the of is a in the and of been extensively in the of the but is involved in the of and of and in the of GIP on GIP the of KV1.4 and for the in KV1.4 peak in the of KV1.4 and in ionic of KV1.4 by HEK293 and for the of for and for KV1.4 by and The the of and the the of of KV1.4 by HEK293 and for and and a the and the HEK293 and for the of GIP in the of the peak and in the and the the and the in of we the and of KV1.4 in The channels and in cells, and on and GIP but the and the and for the effects of GIP on KV1.4 channel is involved in of HEK293 the and for GIP in the and GIP in the and a the and the in channels have been role in the regulation of glucose-dependent insulin secretion in in KV1.4 is in pancreatic a A-type potassium and GIP in a in A-type peak a in KV1.4 in and The of GIP on peak by and by A-type in is by a channel of in in in A-type potassium A-type potassium channels of KV1.4 channels of peak by in less KV1.4 and The by the A-type in is by and GIP is on peak in a channel in of KV1.4 in by and KV1.4 and and and for of KV1.4 in pancreatic by in and KV1.4 and insulin and a the and the by depolarization for a of of in in of in A-type peak in the peak of on A-type in the and the The of KV1.4 in the of GIP on of KV1.4 GIP of insulin the is KV1.4 in and channel by The A-type the of KV1.4 in in GIP membrane of glucose KV1.4 by GIP in the of but of KV1.4 channels reduced insulin of a of the GIP insulin secretion in the of glucose in glucose GIP in insulin secretion in GIP of KV1.4 channels cells, the of of KV1.4 is of insulin in the of GIP on insulin of KV1.4 by and GIP for for and for KV1.4 by and The the of and the the of insulin GIP and for in glucose the by the and of a the glucose glucose and glucose of GIP insulin secretion in pancreatic been depolarization and in the direct effects on insulin channels the of membrane in cells, and membrane of the of the channel In pancreatic insulin secretion is by the of ionic the potassium potassium the ATP-sensitive (KATP) channel and calcium-activated and voltage-gated (KV) The mechanisms involved in the regulation of and channels in pancreatic have been extensively studied, but less is known about the channels for is role and mechanisms involved in regulating The the of the incretin GIP and GIP effects on pancreatic by a is a of the The by GIP on insulin secretion in of the HEK293 the and we have GIP peak of KV1.4 channels a by the of and the In of and in the of KV1.4 the of in effects on KV1.4 by KV1.4 channels by and peak in GIP and in is by the and of membrane channel and and of channel of channel by and been a by channels The potassium channel the of a voltage-gated channel by and a of and channels have been by and a of potassium channels have the effects of of the of KV1.4 on been the of KV1.4 by in the of a been a in the of peak by a in the mechanisms underlying the effects of on channel the is in channel In the present study, GIP reduced KV1.4 peak of KV1.4 and of the by in a in KV1.4 peak mechanisms of of channels is of the involved in the of membrane The regulation of of channels in the membrane the of and of the channel of the channel the and by and a by the but is for the regulation of a of membrane is a of of by of channels in ionic In the present study, direct of KV1.4 by is involved in of the channel and of KV1.4 in peak GIP and and involved in In the KV1.4 of the role by in of KV1.4 The underlying by is of KV1.4 is the present of channel by and of channel channel and involved in the KV1.4 channel present in pancreatic and GIP A-type ionic have been the of channels in been and KV1.4 by in and present the and by a for In the study, we have KV1.4 is in pancreatic in channel is the of A-type potassium on pancreatic A-type role in the of of insulin secretion and by in the of glucose is the of A-type by KV1.4 in pancreatic the and of in the of insulin is by the of KV1.4 channels in in insulin secretion in and of a of KV1.4 channel in and of ionic peak is by GIP insulinotropic the of a of The effects of GIP and for of the insulin a and is a of of is for the of for insulinotropic polypeptide (GIP) glucose-dependent insulinotropic GIP ATP-sensitive calcium-activated voltage-gated glucose-dependent insulinotropic GIP ATP-sensitive calcium-activated voltage-gated and the involved in the of insulin secretion a insulin secretion is of ATP-sensitive (KATP) channels in membrane of and in by membrane by (KV) and (KCA) channels by potentiating the events underlying membrane depolarization in exerting direct effects on exocytosis. events incretin and of In the of of the and of and is known the of on membrane of the potassium channels the of channels of and involved in of of of in of channels the pancreatic the of and insulin have been and in and of potassium on the of and A-type by is by and and A-type is by KV1.4 of present in pancreatic of the have on the The on a role for GIP in the regulation of a of the and of channel potassium involved in the regulation of insulin cells, we GIP peak of KV1.4 a In KV1.4 in pancreatic and GIP A-type potassium in GIP and of KV1.4 and in of a in reduced insulin insulin the of for a role for of of the channel in the of insulin of a in and and pancreatic GIP of the for the and by and by of KV1.4 and in the and by and for the the a of in the of the KV1.4 the of a the The and the and in by and the by for and the by in and the a and reduced KV1.4 In in a of of and the of of and a of of the of of of KV1.4 for by the the on and the for of on a and of the KV1.4 and by and the of and the The of the of and on in in and ionic we a the The the and and and a of HEK293 for a of a for KV1.4 a the GIP for of and and for The and by and by and and of the and by of and for GIP and and a and a in and in in for in of and a for a for KV1.4 and The KV1.4 and insulin and and and a the by in glucose and a of the of for the the GIP and for in and glucose the a the of in the the and of a in the of a in and and pancreatic GIP of the for the and by and by of KV1.4 and in the and by and for the the a of in the of the KV1.4 the of a the The and the KV1.4 and in by and the by for and the by in and the a and reduced KV1.4 In in a of of and the of of and a of of the of of of KV1.4 for by the the on and the for of on a and of the KV1.4 and by and the of and the The of the of and on in in and ionic we a the The the and and and a of HEK293 for a of a for KV1.4 a the GIP for of and and for The and by and by and and of the and by of and for GIP and and a and a in and in in for in of and a for a for KV1.4 and The KV1.4 and insulin and and and a the by in glucose and a of the of for the the GIP and for in and glucose the a the of in the the and of a in the of KV1.4 in HEK293 in the of KV1.4 by GIP HEK293 a of the The KV1.4 in of in a in peak and by and The in peak in HEK293 cells, the in the of GIP The of GIP a of KV1.4 GIP the of in GIP the of GIP GIP the of GIP is by in the of in and in the of KV1.4 involved in the of KV1.4 peak by GIP The in KV1.4 peak of and is a GIP involved in the regulation of insulin of GIP in of GIP GIP of of in KV1.4 peak and of The and and the of KV1.4 peak the the of GIP on KV1.4 peak is involved in the regulation of in the of KV1.4 and in KV1.4 KV1.4 the of and in of KV1.4 the of and for and of KV1.4 the of for the of the of KV1.4 involved in GIP in KV1.4 the in the The been of of the channel GIP the peak by the the GIP the in KV1.4 is for of the of the of KV1.4 involved in regulating and The is for and membrane of the channel and the is the for and we a in the of of KV1.4 is in on the of for of the and and in of the by GIP peak and but The in the membrane of KV1.4 by is the in peak and of in the is a in in the of KV1.4 and in ionic and in of KV1.4 by of KV1.4 for the of in of in the of and The by in and by The and of the KV1.4 and the for and of and GIP and peak and In the of of and of GIP and the in of KV1.4 by of KV1.4 for in of in the of in and the for and the and of and and peak and the of of and the of GIP and the the and the in KV1.4 of channels been in in is in and in peak involved in and in KV1.4 peak by endocytosis. the of KV1.4 GIP The on is the is of KV1.4 channels in the a channel is in membrane of KV1.4 GIP and of KV1.4 channels present in the membrane reduced by GIP in KV1.4 peak by on GIP in the of is a in the and of been extensively in the of the but is involved in the of and of and in the of GIP on GIP the of KV1.4 and for the in KV1.4 peak in the of KV1.4 and in ionic of KV1.4 by HEK293 and for the of for and for KV1.4 by and The the of and the the of of KV1.4 by HEK293 and for and and a the and the HEK293 and for the of GIP in the of the peak and in the and the the and the in of we the and of KV1.4 in The channels and in cells, and on and GIP but the and the and for the effects of GIP on KV1.4 channel is involved in of HEK293 the and for GIP in the and GIP in the and a the and the in channels have been role in the regulation of glucose-dependent insulin secretion in in KV1.4 is in pancreatic a A-type potassium and GIP in a in A-type peak a in KV1.4 in and The of GIP on peak by and by A-type in is by a channel of in in in A-type potassium A-type potassium channels of KV1.4 channels of peak by in less KV1.4 and The by the A-type in is by and GIP is on peak in a channel in of KV1.4 in by and KV1.4 and and and for of KV1.4 in pancreatic by in and KV1.4 and insulin and a the and the by depolarization for a of of in in of in A-type peak in the peak of on A-type in the and the The of KV1.4 in the of GIP on of KV1.4 GIP of insulin the is KV1.4 in and channel by The A-type the of KV1.4 in in GIP membrane of glucose KV1.4 by GIP in the of but of KV1.4 channels reduced insulin of a of the GIP insulin secretion in the of glucose in glucose GIP in insulin secretion in GIP of KV1.4 channels cells, the of of KV1.4 is of insulin in the of GIP on insulin of KV1.4 by and GIP for for and for KV1.4 by and The the of and the the of insulin GIP and for in glucose the by the and of a the glucose glucose and glucose GIP of KV1.4 in HEK293 in the of KV1.4 by GIP HEK293 a of the The KV1.4 in of in a in peak and by and The in peak in HEK293 cells, the in the of GIP The of GIP a of KV1.4 GIP the of in GIP the of GIP GIP the of GIP is by in the of GIP in and in the of KV1.4 involved in the of KV1.4 peak by GIP The in KV1.4 peak of and is a GIP involved in the regulation of insulin of GIP in of GIP GIP of of in KV1.4 peak and of The and and the of KV1.4 peak the the of GIP on KV1.4 peak is involved in the regulation of in the of KV1.4 and in KV1.4 KV1.4 the of and in of KV1.4 the of and for and of KV1.4 the of for the of the of KV1.4 involved in GIP in KV1.4 the in the The been of of the channel GIP the peak by the the GIP the in KV1.4 is for of the of the of KV1.4 involved in regulating and The is for and membrane of the channel and the is the for and we a in the of of KV1.4 is in on the of for of the and and in of the by GIP peak and but The in the membrane of KV1.4 by is the in peak and of in the is a in in KV1.4 of channels been in in is in and in peak involved in and in KV1.4 peak by endocytosis. the of KV1.4 GIP The on is the is of KV1.4 channels in the a channel is in membrane of KV1.4 GIP and of KV1.4 channels present in the membrane reduced by GIP in KV1.4 peak by on GIP in the of is a in the and of been extensively in the of the but is involved in the of and of and in the of GIP on GIP the of KV1.4 and for the in KV1.4 peak in of we the and of KV1.4 in The channels and in cells, and on and GIP but the and the and for the effects of GIP on KV1.4 channel in channels have been role in the regulation of glucose-dependent insulin secretion in in KV1.4 is in pancreatic a A-type potassium and GIP in a in A-type peak a in KV1.4 in and The of GIP on peak by and by A-type in is by a channel of in in in A-type potassium A-type potassium channels of KV1.4 channels of peak by in less KV1.4 and The by the A-type in is by and GIP is on peak in a of KV1.4 in the of GIP on of KV1.4 GIP of insulin the is KV1.4 in and channel by The A-type the of KV1.4 in in GIP membrane of glucose KV1.4 by GIP in the of but of KV1.4 channels reduced insulin of a of the GIP insulin secretion in the of glucose in glucose GIP in insulin secretion in GIP of KV1.4 channels cells, the of of KV1.4 is of insulin of GIP insulin secretion in pancreatic been depolarization and in the direct effects on insulin channels the of membrane in cells, and membrane of the of the channel In pancreatic insulin secretion is by the of ionic the potassium potassium the ATP-sensitive (KATP) channel and calcium-activated and voltage-gated (KV) The mechanisms involved in the regulation of and channels in pancreatic have been extensively studied, but less is known about the channels for is role and mechanisms involved in regulating The the of the incretin GIP and GIP effects on pancreatic by a is a of the The by GIP on insulin secretion in of the HEK293 the and we have GIP peak of KV1.4 channels a by the of and the In of and in the of KV1.4 the of in effects on KV1.4 by KV1.4 channels by and peak in GIP and in is by the and of membrane channel and and of channel of channel by and been a by channels The potassium channel the of a voltage-gated channel by and a of and channels have been by and a of potassium channels have the effects of of the of KV1.4 on been the of KV1.4 by in the of a been a in the of peak by a in the mechanisms underlying the effects of on channel the is in channel In the present study, GIP reduced KV1.4 peak of KV1.4 and of the by in a in KV1.4 peak mechanisms of of channels is of the involved in the of membrane The regulation of of channels in the membrane the of and of the channel of the channel the and by and a by the but is for the regulation of a of membrane is a of of by of channels in ionic In the present study, direct of KV1.4 by is involved in of the channel and of KV1.4 in peak GIP and and involved in In the KV1.4 of the role by in of KV1.4 The underlying by is of KV1.4 is the present of channel by and of channel channel and involved in the KV1.4 channel present in pancreatic and GIP A-type ionic have been the of channels in been and KV1.4 by in and present the and by a for In the study, we have KV1.4 is in pancreatic in channel is the of A-type potassium on pancreatic A-type role in the of of insulin secretion and by in the of glucose is the of A-type by KV1.4 in pancreatic the and of in the of insulin is by the of KV1.4 channels in in insulin secretion in and of a of KV1.4 channel in and of ionic peak is by GIP insulinotropic the of a of The effects of GIP and for of the insulin a and is a of of is for the of for The of GIP insulin secretion in pancreatic been depolarization and in the direct effects on insulin channels the of membrane in cells, and membrane of the of the channel In pancreatic insulin secretion is by the of ionic the potassium potassium the ATP-sensitive (KATP) channel and calcium-activated and voltage-gated (KV) The mechanisms involved in the regulation of and channels in pancreatic have been extensively studied, but less is known about the channels for is role and mechanisms involved in regulating The the of the incretin GIP and GIP effects on pancreatic by a is a of the The by GIP on insulin secretion in of the HEK293 the and we have GIP peak of KV1.4 channels a by the of and the In of and in the of KV1.4 the of in effects on KV1.4 by KV1.4 channels by and peak in GIP and The in is by the and of membrane channel and and of channel of channel by and been a by channels The potassium channel the of a voltage-gated channel by and a of and channels have been by and a of potassium channels have the effects of of the of KV1.4 on been the of KV1.4 by in the of a been a in the of peak by a in the mechanisms underlying the effects of on channel the is in channel In the present study, GIP reduced KV1.4 peak of KV1.4 and of the by in a in KV1.4 peak mechanisms of The of channels is of the involved in the of membrane The regulation of of channels in the membrane the of and of the channel of the channel the and by and a by the but is for the regulation of a of membrane is a of of by of channels in ionic In the present study, direct of KV1.4 by is involved in of the channel and of KV1.4 in peak GIP and and involved in In the KV1.4 of the role by in of KV1.4 The underlying by is of KV1.4 is the present of channel by and of channel channel and involved in the The KV1.4 channel present in pancreatic and GIP A-type ionic have been the of channels in been and KV1.4 by in and present the and by a for In the study, we have KV1.4 is in pancreatic in channel is the of A-type potassium on pancreatic A-type role in the of of insulin secretion and by in the of glucose is the of A-type by KV1.4 in pancreatic the and of in the of insulin is by the of KV1.4 channels in in insulin secretion in and of a In of KV1.4 channel in and of ionic peak is by GIP insulinotropic the of a of The effects of GIP and for of the insulin a and is a of of is for the of for for

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.