Insulin May Help Restore Neurocognitive Issues in HIV Patients

Insulin may prove to be beneficial for more than just patients with diabetes. In a study using HIV mouse models, investigators found that delivering insulin intranasally helped prevent neuroinflammation, neuronal injury, and restored neurobehavioral function.

HIV-associated neurocognitive disorders (HAND) represent a spectrum disorder of neurocognitive dysfunctions that result from HIV infection. Even individuals on antiretroviral therapy are at-risk of developing neurocognitive dysfunction.

In new study published in the Journal of Neuroscience, the authors sought to examine the actions of insulin using ex vivo and in vivo models of HAND.

The investigators observed an increased neuroinflammatory gene expression in brains of patients with HIV/AIDS. The insulin receptor was detected on both neurons and glia, but its expression remained unaffected by the virus, according to the authors.

The results of the study showed that insulin treatment of HIV-infected primary human microglia suppressed supernatant HIV-1 p24 levels, reduced CXCL10 and IL-6 transcript levels, and induced peroxisome proliferator-activated receptor gamma (PPAR-γ) expression.

Furthermore, insulin treatment of primary human neurons prevented HIV-1 Vpr-mediated cell process retraction and death. In cats with feline immunodeficiency virus (FIV), daily intranasal insulin treatment reduced CXCL10, IL-6, and FIV RNA detection in the brain, although PPAR-γ in glia was increased compared with PBS-treated FIV⁺ control animals.

In addition to the molecular changes, the investigators observed the diminishing of glial activation in the cerebral cortex and white matter of FIV-positive animals treated with insulin, with associated preservation of cortical neurons.

The neuronal counts in parietal cortex, striatum, and the hippocampus were found to be higher in the FIV-positive insulin-treated group compared with the FIV-positive PBS-treated group. Furthermore, the intranasal insulin treatment was found to improve neurobehavioral performance, including memory and motor functions, in the animals with FIV.

“Insulin exerted ex vivo and in vivo antiviral, anti-inflammatory, and neuroprotective effects in models of HAND, representing a new therapeutic option for patients with inflammatory or infectious neurodegenerative disorders including HAND,” the authors concluded.