Pancreatic nerves across species: Anatomical and functional disparities and their metabolic ramifications

Abstract

Pancreatic nerves exhibit significant anatomical and functional disparities across species, with profound implications for metabolism and clinical practices like pancreatic transplantation and disease treatment. In humans, pancreatic nerves feature a complex distribution of sympathetic and parasympathetic fibers, forming intricate plexuses that closely interact with surrounding organs, playing a crucial role in regulating both endocrine (e.g., insulin and glucagon release) and exocrine secretions to maintain metabolic balance. Rodents, such as rats and mice-common experimental models-have relatively simpler pancreatic nerve architectures; for instance, mice show more concentrated nerve fibers around islets, while rats display greater variability in nerve density across pancreatic regions, which influences their responses to metabolic stimuli and makes them valuable but not fully analogous to human models. Canines and felines, often used in translational studies, possess pancreatic nerve systems that share some similarities with humans, such as comparable nerve plexus organization, yet differ in fiber type proportions, affecting their susceptibility to metabolic abnormalities like pancreatitis-related glucose dysregulation. These species-specific differences in pancreatic nerves directly impact metabolic processes: In humans, impaired nerve function is linked to metabolic disorders like diabetes and obesity, whereas in animal models, variations in neural control of hormone release and pancreatic homeostasis lead to differences in disease progression and response to interventions. Understanding these discrepancies is vital: It not only helps interpret findings from animal studies when translating to human therapies but also guides pancreatic transplantation by highlighting the need for species-specific considerations in nerve reconstruction to restore metabolic function, and identifies potential therapeutic targets tailored to the unique neural-metabolic interactions of each species.

Keywords: Pancreatic nerves; Species differences; Autonomic innervation; Sympathetic nervous system; Parasympathetic nervous system; Islets of langerhans; Metabolic regulation; Diabetes; Pancreatic transplantation; Rodent models

Core Tip: This review highlights the significant anatomical and functional disparities in pancreatic innervation across humans, rodents, canines, and felines. These species-specific differences profoundly impact metabolic regulation, disease susceptibility (e.g., diabetes, pancreatitis), and responses to therapeutic interventions. Understanding these variations is crucial for accurately translating findings from animal models to human clinical applications, particularly in areas like pancreatic transplantation where nerve reconstruction strategies must be species-appropriate. Recognizing the unique neuro-metabolic interactions in each species can guide the development of more effective, tailored therapies for metabolic disorders and improve the predictive value of preclinical research.