Fig. 1

Schematic overview of the consensus model of mitochondria and glycolysis cooperation in glucose-stimulated insulin secretion (GSIS). Glucose is phosphorylated by glucokinase and converted to pyruvate by glycolysis. Pyruvate preferentially enters the mitochondria and fuels the TCA cycle, resulting in the transfer of reducing equivalents to the respiratory chain, leading to hyperpolarization of the mitochondrial membrane (ΔΨm↑) and generation of ATP. Subsequently, closure of KATP- channels depolarizes the cell membrane (ΔΨc↓). This opens voltage-gated Ca²⁺ channels, raising the cytosolic Ca²⁺ concentration, which triggers insulin exocytosis. ER-mitochondria interaction has been proposed to participate in the metabolism–secretion coupling. Ca2⁺ is transferred from ER to mitochondria through inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel 1 (VDAC1)