ArticleNeurobiology of disease2025
Pancreatic hypersecretion of amyloid-forming human amylin dysregulates the neuro-immune axis and B cell development in a model of type-2 diabetes.
Article in Neurobiology of disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.
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1 citing paper in PubMed, 1 synthesis or guideline pooled it.
- Altered cortical thickness in type 2 diabetes mellitus patients revealed by coordinate-based meta-analysis.BMC endocrine disorders · 2026Pooled it
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15 authors.
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Abstract
During Type 2 diabetes (T2D), the immune system becomes dysregulated, adopting a pro-inflammatory phenotype and secreting cytokines that exacerbate inflammation. Human amylin (i.e., islet amyloid polypeptide) secreted from the pancreas of HIP rats during T2D has been shown to deposit in the microvasculature and lead to neurodegeneration and cognitive decline. Although T2D is linked to neuroinflammation and cognitive impairment, whether and how peripheral immune changes, driven in part by amyloidogenic amylin deposition, shape these outcomes is not well understood. We investigated how the accumulation of pancreatic human amylin impacts the peripheral and neuroimmune response in transgenic rat and mouse models with endogenous overexpression. In rats, hypersecretion of pancreatic human amylin reduced adaptive and innate immune cells in the spleen and brain, the latter associated with the downregulation of cerebrovascular ICAM-1, which is responsible for immune cell migration into the brain. Acute systemic injections of aggregated human amylin in wild-type (WT) rats led to immune alterations in the blood only, suggesting brain-specific changes may require chronic exposure. In mice that hypersecrete pancreatic human amylin, we identified defects in B cell development, including reduced B cell populations in the spleen and bone marrow. This immune dysregulation was associated with upregulated CXCR4 expression in precursor B cells, suggesting a potential mechanism for systemic B cell losses during chronic T2D. To further support these findings in human disease, single-cell sequencing of patients with T2D revealed elevated CXCR4 expression across multiple B cell subsets, highlighting the relevance of this axis in diabetic immune dysregulation. Taken together, our findings indicate that T2D-associated amylin may contribute to T2D by altering both peripheral and neuroimmune responses. Moreover, the CXCL12/CXCR4 signaling axis emerges as a promising target for immunotherapeutic strategies to mitigate type-2 diabetic cognitive decline and neurodegeneration.
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