Abstract
In this account of the 2022 Palade Medal Lecture, an attempt is made to explain, as simply as possible, the most essential features of normal physiological control of pancreatic enzyme secretion, as they have emerged from more than 50 years of experimental work. On that basis, further studies on the mechanism by which acute pancreatitis is initiated are then described. Calcium ion signaling is crucially important for both the normal physiology of secretion control as well as for the development of acute pancreatitis. Although acinar cell processes have, rightly, been central to our understanding of pancreatic physiology and pathophysiology, attention is here drawn to the additional critical influence of calcium signaling events in stellate and immune cells in the acinar environment. These signals contribute significantly to the crucially important inflammatory response in acute pancreatitis.