AI Article Synopsis
- The study investigates the role of perineuronal nets (PNNs) around glucoregulatory neurons in the arcuate nucleus of the hypothalamus, particularly in relation to type 2 diabetes (T2D).
- In the Zucker diabetic fatty (ZDF) rat model, PNN abundance is significantly lower compared to healthy rats, and this reduction is linked to changes in specific sulfation patterns of chondroitin sulfate glycosaminoglycans in the mediobasal hypothalamus.
- A single injection of fibroblast growth factor 1 (FGF1) not only replenishes PNNs but also prolongs diabetes remission, suggesting that these matrix structures play a crucial role in
Article Abstract
We recently showed that perineuronal nets (PNNs) enmesh glucoregulatory neurons in the arcuate nucleus (Arc) of the mediobasal hypothalamus (MBH), but whether these PNNs play a role in either the pathogenesis of type 2 diabetes (T2D) or its treatment remains unclear. Here we show that PNN abundance within the Arc is markedly reduced in the Zucker diabetic fatty (ZDF) rat model of T2D, compared with normoglycaemic rats, correlating with altered PNN-associated sulfation patterns of chondroitin sulfate glycosaminoglycans in the MBH. Each of these PNN-associated changes is reversed following a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) at a dose that induces sustained diabetes remission in male ZDF rats. Combined with previous work localizing this FGF1 effect to the Arc area, our finding that enzymatic digestion of Arc PNNs markedly shortens the duration of diabetes remission following icv FGF1 injection in these animals identifies these extracellular matrix structures as previously unrecognized participants in the mechanism underlying diabetes remission induced by the central action of FGF1.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572652 | PMC |
| http://dx.doi.org/10.1038/s42255-020-00275-6 | DOI Listing |
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