The Neuro‐Pancreatic Axis in Metabolic Disease: A Review of Neuro‐Immune Interfaces and Translational Challenges

ABSTRACT

The idea of standard glucose regulation emphasizes the feedback mechanisms of the Langerhans islets. The neuro‐pancreatic axis, comprising the central nervous system, autonomic networks, and intrapancreatic ganglia, serves as a crucial regulatory element, as evidenced by increasing data. In metabolic and neurodegenerative disorders, neuro‐immune‐endocrine connections diminish. Excessive nutrition and hypothalamic neuroinflammation may induce autonomic dysfunction in type 2 diabetes and obesity. The dysfunction progresses from a compensatory phase characterized by parasympathetic hyperactivation to a decompensated state dominated by sympathetic activity, resulting in β‐cell exhaustion and persistent hepatic gluconeogenesis. Type 1 diabetes initiates with an early autoimmune assault on peri‐islet Schwann cells and intrapancreatic nerves, disrupting the neuro‐glial barrier and permitting leukocyte infiltration prior to β‐cell demise. Alzheimer's and Parkinson's have pathophysiological similarities with diabetes, as central insulin resistance and autonomic neuronal atrophy directly impair islet secretory function. Interspecies differences, exemplified by the diminished cholinergic innervation and the predominance of peptidergic innervation in human islets relative to rat models, impede the practical implementation of these molecular discoveries. Contemporary in vitro technologies, such as human islet organoids, are deficient in spatial neuronal integration, hindering their ability to effectively replicate neuroendocrine interactions, which is crucial for understanding the complex interplay between the nervous system and pancreatic function in diabetes research. This review emphasizes the imperative transition from glucocentric to neurometabolic restorative therapy. Targeted neuromodulation, bioelectronic devices, and the simultaneous hormonal‐neuromodulatory effects of GLP‐1 receptor agonists may stabilize the neuro‐pancreatic axis and maintain integrated endocrine function.