How does blood glucose regulate insulin secretion by pancreatic β cells?
A.
When blood glucose rises, GLUT2 transporters carry glucose into the β cells, where it is immediately converted to glucose 6-phosphate by glucokinase and enters glycolysis.
B.
With the higher rate of glucose catabolism, 2 [ATP] increases, causing the closing of ATP-gated K + channels in the plasma membrane. Reduced efflux of K + depolarizes the membrane. Membrane depolarization opens voltage-gated Ca 2+ channels, and the resulting increase in cytosolic [Ca 2+ ] triggers the release of insulin by exocytosis.
C.
The brain integrates inputs on energy supply and demand, and signals from the parasympathetic and sympathetic nervous systems also affect (stimulate and inhibit, respectively) insulin release.
D.
A simple feedback loop limits hormone release: insulin lowers blood glucose by stimulating glucose uptake by the tissues; the reduced blood glucose is detected by the β cell as a diminished flux through the glucokinase reaction; this slows or stops the release of insulin. This feedback regulation holds blood glucose concentration nearly constant despite large fluctuations in dietary intake.