Endogenous insulin directly protects pancreatic acinar cells in pancreatitis

Diabetes is known to predispose patients to the development of the life-threatening disorder pancreatitis and to cause a more severe course of pancreatitis. However, the mechanistic link between diabetes and pancreatitis is not clear. Aberrant cytosolic Ca²⁺ signals within the main parenchymal cell of the pancreas, the acinar cells, are central to the initiation of pancreatitis and can modulate its severity. The acinar cell Ca²⁺ signals are tightly regulated by a Ca²⁺ toolbox, which includes the plasma membrane Ca²⁺-ATPase (PMCA). A new paper by Bruce et al. shows that active extrusion of Ca²⁺through the PMCA protects acinar cells against the damage of pancreatitis in the setting of diabetes. The novelty of the finding here is that insulin receptors on the acinar cell transduce a glycolytic supply of ATP to fuel the PMCA and, thereby, link diabetes to pancreatitis through Ca²⁺signaling.