Figure 2.

Graphical summary of the consequences of the β-cell-specific presenilin-1-mediated ER Ca²⁺ leak. Ca²⁺ leaking out of the ER is directly sequestered to mitochondria, leading to increased basal matrix Ca²⁺ levels, where it pre-stimulates the Ca²⁺-dependent dehydrogenases of the citric acid cycle, augmenting resting organelle ATP levels. ATP-sensitive K⁺-channels are inhibited leading to cellular depolarization. This electrochemical shift triggers Ca²⁺ uptake via L-type Ca²⁺ channels. As a result, Ca²⁺-induced Ca²⁺ release is initiated, promoting insulin exocytosis into the extracellular space.