CARD9 Conveys Pancreatic Islet Sympathetic Nervous β2 Signals to Reshape Macrophage Creatine Metabolism in Type 1 Diabetes.

ABSTRACT: Type 1 diabetes (T1D) is an autoimmune disorder marked by the injury of pancreatic β cells, during which sympathetic neurons in the endocrine region of pancreas are lost, whereas those in the exocrine regions surrounding islets remain intact. This abnormal sympathetic nervous signaling may disrupt the balance of the neuroendocrine-immune network and contribute to the development of T1D, although its underlying molecular mechanisms are still elusive. Here, single-cell omics and whole-tissue immunostaining reveal a decrease in pancreatic sympathetic nerve density in T1D patients and T1D mouse models. Surgical and chemical desensitization of the sympathetic nervous system exacerbates T1D, while macrophage depletion mitigates this effect. Mechanistically, diminished norepinephrine (NE) release

SUBMITTER: Yuan H 

PROVIDER: S-EPMC12806524 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature