Overview of exocrine pancreatic pathobiology

Abstract

Exocrine pancreas is a source of several enzymes that are essential for the digestive process. The exocrine pancreatic secretion is tightly regulated by the neuroendocrine system. The endocrine pancreas is tightly integrated anatomically and physiologically with the exocrine pancreas and modulates its function. Compound-induced pancreatitis is not a common event in toxicology or drug development, but it becomes a significant liability when encountered. Understanding the species-specific differences in physiology is essential to understand the underlying pathobiology of pancreatic disease in animal models and its relevance to human disease. This review will mainly focus on understanding the morphology and physiology of the pancreas, unique islet-exocrine interactions, and pancreatitis.

Keywords: animal models; digestive system; endocrine system..

Figure 1

An artist’s rendering of the vasculature within the rat pancreas. The islets and acini have a tightly integrated blood supply. The islets may be located intralobular or interlobular and have corresponding blood supply. The blood draining from the intralobular islets pass through the exocrine acini before joining the venous system. The peptides from the islets contributes to the regulation of peri-islet acini (please see text for more details). (Adapted from Murakami and Fujita, 1992)

Figure 2

Cholecystokinin (CCK) stimulation of the exocrine pancreas is species dependent. In rodents, CCK released from the I cells within the intestine enter the circulation and directly stimulate the CCK1 receptors on the exocrine acini to stimulate secretions. In addition, CCK can also activate the sensory nerve fibers resulting in the activation of long vago-vagal and short enteropancreatic cholinergic reflexes. However, in humans, the latter process is the most accepted physiological process of exocrine stimulation. (Adapted from Wang and Cui, 2007)