Year: 2026
Type: preprint
Abstract: Diabetic peripheral neuropathy (DPN) is a major complication of diabetes that profoundly affects quality of life, yet its cellular mechanisms remain poorly defined. Neuropathic pain and sensory loss in DPN are thought to arise from progressive alterations in peripheral nerves usually described as a glove-stocking distribution, but the specific contribution of sensory neuron subtypes has received little attention. Here, we focused on Aβ rapidly adapting low-threshold mechanoreceptors (Aβ RA-LTMRs), a large-diameter sensory neuron subtype best known for mediating touch and vibratory sensation. Using an intersectional genetic approach, we generated Advillin Cre ; MafA FlpO ; Ai65 mice, allowing us to selectively label MafA-expressing sensory neuronal populations, which we identified as Aβ RA-LTMRs. We provide the first detailed characterization of how diet-induced type 2 diabetes alters Aβ RA-LTMRs. After 16 weeks of high-fat diet (HFD), we observed striking sex-dependent effects. Male mice developed impaired glucose tolerance, mechanical hypoalgesia, and thermal hyperalgesia, which correlated with a decrease of Aβ RA-LTMR central projections in the dorsal horn. By contrast, female mice showed no changes in either their glycemic status or their sensory sensitivity. These findings demonstrate that Aβ RA-LTMRs are vulnerable to early diabetes-induced alterations in a sex-dependent manner and highlight distinct peripheral versus central mechanisms contributing to sensory dysfunction.
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7223559393