Figure 1

Schematic diagram of biochemical pathways involved in energy metabolism and Ca²⁺ handling in the pancreatic β -cell. Glucose equilibrates across the plasma membrane and is phosphorylated by glucokinase to glucose 6-phosphate, which initiates glycolysis. Lactate dehydrogenase (LDH) converts a portion of pyruvate to lactate. Pyruvate produced by glycolysis preferentially enters the mitochondria and is metabolized in the tricarboxylic acid (TCA) cycle, which then yields reducing equivalents in the form of NADH and FADH2. The transfer of electrons from these reducing equivalents through the mitochondrial electron transport chain is coupled with the pumping of protons from the mitochondrial matrix to the intermembrane space. The resulting transmembrane electrochemical gradient drives the ATP synthesis at ATP-synthase. Part of the protons may leak back through uncoupling proteins (UCPs). The shuttle systems are required for the transfer of reducing equivalents from the cytoplasm to the mitochondrial matrix. Calcium handling proteins such as the uniporter and Na⁺/Ca²⁺ exchanger regulate Ca²⁺ handling in mitochondria. ATP is transferred to the cytosol, raising the ATP/ADP ratio. This results in the closure of the ATP sensitive K⁺ channels (katp), which in turn leads to depolarization of the cell membrane. In response, the voltage-sensitive Ca²⁺ channels open, promoting calcium entry and increasing the cytoplasmic Ca²⁺. ATP_c and ADP_free are the free cytosolic form of ATP and ADP, G3P is the glyceraldehydes 3-phosphate, PDH is the pyruvate dehydrogenase, ANT is the adenine nucleotide translocase, Ψ_m is the mitochondrial membrane potential. Solid lines indicate flux of substrates, and dashed lines indicate regulating effects, where (+) represents activation and (-) repression.