Hypothalamic perineuronal net assembly is required for sustained diabetes remission induced by fibroblast growth factor 1 in rats

Nat Metab. 2020 Oct;2(10):1025-1033. doi: 10.1038/s42255-020-00275-6. Epub 2020 Sep 7.


We recently showed that perineuronal nets (PNNs) enmesh glucoregulatory neurons in the arcuate nucleus (Arc) of the mediobasal hypothalamus (MBH)1, 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 area2-4, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Animals
  • Blood Glucose
  • Body Weight
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 2 / drug therapy
  • Eating
  • Extracellular Matrix*
  • Fibroblast Growth Factor 1 / administration & dosage
  • Fibroblast Growth Factor 1 / therapeutic use*
  • Humans
  • Hypothalamus / physiopathology*
  • Injections, Intraventricular
  • Male
  • Middle Aged
  • Neurons*
  • Rats
  • Rats, Wistar
  • Rats, Zucker
  • Young Adult


  • Blood Glucose
  • Fibroblast Growth Factor 1