Schematic diagram of the new β-cell model. The model includes ion fluxes through the plasma membrane, Ca²⁺ dynamics including the ER, and [G]-dependent ATP synthesis in mitochondria. The ion fluxes include voltage-dependent Ca²⁺ current (I_CaV), delayed rectifier K⁺ current (I_KDr), Ca²⁺-activated nonselective cation current (I_TRPM), store-operated current (I_SOC), V- and [Ca²⁺]_i-dependent transient outward K⁺ current (I_KCa(BK)), ATP-sensitive K⁺ current (I_KATP), Ca²⁺-activated K⁺ current (I_KCa(SK)), background nonselective cation current (I_bNSC), PMCA current (I_PMCA), NCX current (I_NaCa), and NaK current (I_NaK). ER Ca²⁺ dynamics consist of Ca²⁺ uptake by SERCA (J_SERCA) and Ca²⁺ release (J_rel). In the ATP synthesis pathway, Re represents the reduced form of pyridine nucleotide (NADH), and J_glc and J_β,ox represent the glycolysis- and β oxidation–dependent Re production rates, respectively. ATP is synthesized at the expense of Re through oxidative phosphorylation (J_op) and is consumed via Ca²⁺-dependent/-independent pathways (J_c,ATP). The direction of arrows indicates the positive sign of the values calculated by the corresponding equations in the supplemental material.