Schematic overview of the steps linking variations in glucose concentration to variations in insulin secretion. The efficiency
by which variations in glucose concentrations are coupled with the magnitude of the change in ADP/ATP ratio is a main determinant
for insulin secretion. Steps that modulate the efficiency are as follows: the activity of glucokinase (GK); the activity of
lactate dehydrogenase (LDH), which is low in functional β-cells (thin arrows); and the thiamin status of the cell. Thiamin
is a cofactor for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, enzymes that determine the flux of glucose through
glycolysis and the Krebs cycle. The activity of the Krebs cycle is also upregulated by the uptake of Ca2+ by mitochondria after the ATP/ADP-induced closure of the K channel and subsequent opening of the voltage-gated Ca channel.