Vagal nerve innervation divergence in liver/pancreas: A forgotten key to endocrine recovery after transplantation?

Table 1 The distinctions between pancreatic and hepatic innervation

Comparative dimensions	Vagus nerve of the liver	Vagus nerve of the pancreas	Ref.
Structural characteristics	Most vagal nerve fibers travel along with the portal vein-hepatic artery-bile duct (the hepatic hilum/portal triad) and their surrounding structures, forming a general distribution pattern of vascular-biliary associated pathways. The liver lacks intrinsic neurons/ganglia, and its neural regulation relies more on the input of exogenous autonomic nerves (including both vagal afferents and efferents)	The pancreas possesses distinct intrapancreatic ganglia/neural networks, which can project to structures such as acini, ducts and islets of Langerhans. The entry and distribution of nerve fibers are typically characterized by dual perivascular and periductal pathways	[12-15]
Neural components	It comprises both vagal afferents and efferents, and together with sympathetic nerves and spinal afferents, forms the neural input-output framework of the liver. Within the neural pathways of the liver-brain axis, vagal hepatic afferent signals represent a crucial component, which is responsible for transmitting interoceptive information to the brainstem and central nervous system for integration	Vagal efferents: Preganglionic neurons originate from the dorsal motor nucleus of the vagus nerve, project first to the intrapancreatic ganglia, and then cholinergic postganglionic fibers act on target structures such as pancreatic islets. Vagal afferents: The somata of sensory neurons are located in the nodose ganglion, with their fibers projecting back to the relevant brainstem nuclei; spinal afferents are also involved in this process	[8,13,15,16]
Functional characteristics	It further highlights the “perception-central integration-feedback regulation” axis of metabolic status: The liver transmits interoceptive signals including nutritional, metabolic and inflammatory cues to the brain, which contributes to the maintenance of metabolic homeostasis	It further emphasizes the rapid and precise regulation of secretory activities: The vagal pathway is involved in the secretion and regulation of pancreatic islet hormones during the preprandial and prandial phases; its parasympathetic cholinergic inputs can potentiate secretory responses such as insulin release	[16,17]
Innervation characteristics	It is characterized by lower density, weaker local synaptic networks, a higher proportion of afferent signals, and indirect regulation: Owing to the absence of intrinsic ganglia in the liver, the structural basis for local short reflexes is relatively weak, thus rendering the liver more reliant on integrated output regulation at the central level	It is featured by a higher degree of local organization, dense synaptic connections and direct regulatory effects: The hierarchical architecture consisting of preganglionic neurons, intrapancreatic ganglia and postganglionic cholinergic fibers provides the anatomical basis for rapid and highly plastic local regulation	[13,16]