Skip to Main content Skip to Navigation
Journal articles

p-Cresyl sulfate promotes insulin resistance associated with CKD.

Abstract : The mechanisms underlying the insulin resistance that frequently accompanies CKD are poorly understood, but the retention of renally excreted compounds may play a role. One such compound is p-cresyl sulfate (PCS), a protein-bound uremic toxin that originates from tyrosine metabolism by intestinal microbes. Here, we sought to determine whether PCS contributes to CKD-associated insulin resistance. Administering PCS to mice with normal kidney function for 4 weeks triggered insulin resistance, loss of fat mass, and ectopic redistribution of lipid in muscle and liver, mimicking features associated with CKD. Mice treated with PCS exhibited altered insulin signaling in skeletal muscle through ERK1/2 activation. In addition, exposing C2C12 myotubes to concentrations of PCS observed in CKD caused insulin resistance through direct activation of ERK1/2. Subtotal nephrectomy led to insulin resistance and dyslipidemia in mice, and treatment with the prebiotic arabino-xylo-oligosaccharide, which reduced serum PCS by decreasing intestinal production of p-cresol, prevented these metabolic derangements. Taken together, these data suggest that PCS contributes to insulin resistance and that targeting PCS may be a therapeutic strategy in CKD.
Document type :
Journal articles
Complete list of metadatas

Cited literature [35 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00800384
Contributor : Evelyne Vericel <>
Submitted on : Wednesday, March 13, 2013 - 4:06:19 PM
Last modification on : Wednesday, July 8, 2020 - 12:42:51 PM
Long-term archiving on: : Sunday, April 2, 2017 - 12:35:54 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Citation

Laetitia Koppe, Nicolas Pillon, Roxane Vella, Marine Croze, Caroline Pelletier, et al.. p-Cresyl sulfate promotes insulin resistance associated with CKD.. Journal of the American Society of Nephrology, American Society of Nephrology, 2013, 24 (1), pp.88-99. ⟨10.1681/ASN.2012050503⟩. ⟨inserm-00800384⟩

Share

Metrics

Record views

416