Modeling the pancreatic α-cell: dual mechanisms of glucose suppression of glucagon secretion.

ABSTRACT: The mechanism by which glucose induces insulin secretion in β-cells is fairly well understood. Despite years of research, however, the mechanism of glucagon secretion in α-cells is still not well established. It has been proposed that glucose regulates glucagon secretion by decreasing the conductance of either outward ATP-dependent potassium channels (K(ATP)) or an inward store-operated current (SOC). We have developed a mathematical model based on mouse data to test these hypotheses and found that both mechanisms are possible. Glucose metabolism closes K(ATP) channels, which depolarizes the cell but paradoxically reduces calcium influx by inactivating voltage-dependent calcium and sodium channels and decreases secretion. Glucose metabolism also activates SERCA pumps, which fills the endop

SUBMITTER: Watts M 

PROVIDER: S-EPMC3944880 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature