Hypothalamic perineuronal net assembly is required for sustained diabetes remission induced by fibroblast growth factor 1 in rats.
Nat Metab
; 2(10): 1025-1033, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32895577
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator 1 de Crescimento de Fibroblastos
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Diabetes Mellitus Experimental
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Matriz Extracelular
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Hipotálamo
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Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Animals
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Nat Metab
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos