Figure 1. Protective effects of NIM811 in acute pancreatitis.

The cyclophilin D (CypD) inhibitor NIM811 prevents formation of the mitochondrial permeability transition pore (MPTP) that is triggered by a rise in mitochondrial matrix Ca²⁺ concentration. Precipitants of acute pancreatitis (AP) such as bile acids and alcohol non‐oxidative metabolites – fatty acid ethyl esters (FAEE) and fatty acids (FA) – elicit sustained elevations of cytosolic Ca²⁺ in pancreatic acinar and ductal cells that overload mitochondria inducing MPTP formation, loss of membrane potential and ATP production. NIM811 therefore protects against the damaging consequences of aberrant Ca²⁺ signalling and loss of energy provision, maintaining normal physiological function in acinar and ductal cells, thereby ameliorating AP. PMCA, plasma membrane Ca²⁺‐ATPase; SERCA, sarco/endoplasmic reticulum Ca²⁺‐ATPase.