Integrin-associated ILK and PINCH1 protein content are reduced in skeletal muscle of maintenance haemodialysis patients

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • Fulvia Draicchio
  • Stephan van Vliet
  • Oana Ancu
  • Scott A Paluska
  • Kenneth R Wilund
  • Monika Mickute
  • Thozhukat Sathyapalan
  • Derek Renshaw
  • Peter Watt
  • Sylow, Lykke
  • Nicholas A Burd
  • Richard Mackenzie

Muscle atrophy, insulin resistance and reduced muscle PI3K-Akt signaling are common characteristics of patients undergoing maintenance hemodialysis (MHD). Disruption to the transmembrane protein linkage between the cytoskeleton and the extracellular matrix in skeletal muscle may contribute to reduced amino acid metabolism and insulin resistance in MHD patients. Eight MHD patients (age: 56±5 y: BMI: 32±2 kg/m-2) and non-diseased controls (age: 50±2 y: BMI: 31±1 kg/m-2) received primed continuous L-[ring-2H5 ]phenylalanine before consuming a mixed meal. Phenylalanine metabolism was determined using two-compartment modelling. Muscle biopsies were collected prior to the meal and at 300 minutes postprandial. In a separate experiment, skeletal muscle tissue from muscle-specific Rac1 knockout (Rac1 mKO) was harvested to investigate whether Rac1 depletion disrupted the cytoskeleton-integrin linkage, allowing for cross-model examination of proteins of interest.  ILK, PINCH1 and pFAKTyr397 were significantly lower in MHD (< 0.01). Rac1 and Akt showed no difference between groups for the human trial. Rac1 deletion in the Rac1 mKO model did not alter the expression of integrin-associated proteins. Phenylalanine rates of appearance and disappearance , as well as metabolic clearance rates were lower in the MHD group at 30 and 60 min post meal ingestion compared to controls (< 0.05). Both groups showed similar levels of insulin sensitivity and β-cell function. Key proteins in the integrin-cytoskeleton linkage are reduced in MHD patients, suggesting for the first time that integrin-associated proteins dysfunction may contribute to reduced phenylalanine flux without affecting insulin resistance in haemodialysis patients.

OriginalsprogEngelsk
TidsskriftJournal of Physiology
Vol/bind598
Udgave nummer24
Sider (fra-til)5701-5716
Antal sider16
ISSN0022-3751
DOI
StatusUdgivet - 2020

Bibliografisk note

CURIS 2020 NEXS 338

ID: 249065770