IKdelay is related to a novel GLP-1 pathway that is KATP-independent insulin secretion.

点击翻译按钮获取中文摘要

IKdelay in pancreatic β-cells plays important roles in glucose-stimulated insulin secretion. IKdelay current is active during action potentials produced by glucose stimulation. Amplitudes of IKdelay are increased by increasing glucose concentrations from 2.8mM to 16.7mM. These increases were observed only at positive potentials were accompanied by the current decreases in the ranges of negative potentials. Conversely glucose reduction or metabolic inhibition by using FCCP, AMPPNP or 0mM ATP exposure at cytoplasm produced IKdelay increases at negative potentials associated with current decreases at positive potentials. We further observed the similar results in the HEK293 cells expressed with Kv2.1 channels during metabolic inhibition. Exposure to alkaline phosphatase at the cytoplasm showed current increases at negative potentials in Kv2.1 channel-expressed HEK293 cells. Thus, IKdelay changes observed in pancreatic β-cells during metabolic inhibition were resulted from the dephosphorylation of Kv2.1 channels because the channel protein has amino acid residues that can be highly phosphorylated at basal state. We concluded that Kv2.1 channel current is regulated by phosphorylation/dephosphorylation of the channel. These results may suggest that Kv2.1 channel regulation is involved in GLP-1 effect that is revealed with increases insulin secretion in the presence of the hormone.