Hypothalamic perineuronal net assembly is required for sustained diabetes remission induced by fibroblast growth factor 1 in rats
| Autor: | Karl J. Kaiyala, Jarrad M. Scarlett, Gregory J. Morton, Elaine Cabrales, Michael W. Schwartz, Jenny M. Brown, Christina K. Chan, Marie A. Bentsen, Thomas N. Wight, Kimberly M. Alonge, William A. Banks, Zaman Mirzadeh, Aric F. Logsdon, Miklos Guttman |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Arc (protein) Endocrinology Diabetes and Metabolism Perineuronal net Cell Biology Type 2 diabetes FGF1 medicine.disease Fibroblast growth factor chemistry.chemical_compound Endocrinology chemistry Arcuate nucleus Physiology (medical) Internal medicine Diabetes mellitus Internal Medicine medicine Chondroitin sulfate |
| Zdroj: | Nature Metabolism. 2:1025-1033 |
| ISSN: | 2522-5812 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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