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Article Dans Une Revue Diabetes Care Année : 2014

Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization

Francisco J. Ortega
  • Fonction : Auteur
Josep M. Mercader
  • Fonction : Auteur
José Maria Moreno-Navarrete
  • Fonction : Auteur
Oscar Rovira
  • Fonction : Auteur
Ester Guerra
  • Fonction : Auteur
Eduardo Esteve
  • Fonction : Auteur
Gemma Xifra
  • Fonction : Auteur
Cristina Martinez
  • Fonction : Auteur
Wifredo Ricart
  • Fonction : Auteur
Sophie Rome
  • Fonction : Auteur
  • PersonId : 1195256
  • IdHAL : sophie-rome
Monika Karczewska-Kupczewska
  • Fonction : Auteur
Marek Straczkowski
  • Fonction : Auteur
José Manuel Fernández-Real
  • Fonction : Auteur

Résumé

OBJECTIVE: This study sought to identify the profile of circulating microRNAs (miRNAs) in type 2 diabetes (T2D) and its response to changes in insulin sensitivity. RESEARCH DESIGN AND METHODS: The circulating miRNA profile was assessed in a pilot study of 12 men: 6 with normal glucose tolerance (NGT) and 6 T2D patients. The association of 10 circulating miRNAs with T2D was cross-sectionally validated in an extended sample of 45 NGT vs. 48 T2D subjects (65 nonobese and 28 obese men) and longitudinally in 35 T2D patients who were recruited in a randomized, double-blinded, and placebo-controlled 3-month trial of metformin treatment. Circulating miRNAs were also measured in seven healthy volunteers before and after a 6-h hyperinsulinemic-euglycemic clamp and insulin plus intralipid/heparin infusion. RESULTS: Cross-sectional studies disclosed a marked increase of miR-140-5p, miR-142-3p, and miR-222 and decreased miR-423-5p, miR-125b, miR-192, miR-195, miR-130b, miR-532-5p, and miR-126 in T2D patients. Multiple linear regression analyses revealed that miR-140-5p and miR-423-5p contributed independently to explain 49.5% (P \textless 0.0001) of fasting glucose variance after controlling for confounders. A discriminant function of four miRNAs (miR-140-5p, miR-423-5p, miR-195, and miR-126) was specific for T2D with an accuracy of 89.2% (P \textless 0.0001). Metformin (but not placebo) led to significant changes in circulating miR-192 (49.5%; P = 0.022), miR-140-5p (-15.8%; P = 0.004), and miR-222 (-47.2%; P = 0.03), in parallel to decreased fasting glucose and HbA1c. Furthermore, while insulin infusion during clamp decreased miR-222 (-62%; P = 0.002), the intralipid/heparin mixture increased circulating miR-222 (163%; P = 0.015) and miR-140-5p (67.5%; P = 0.05). CONCLUSIONS: This study depicts the close association between variations in circulating miRNAs and T2D and their potential relevance in insulin sensitivity.

Dates et versions

hal-01859430 , version 1 (22-08-2018)

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Citer

Francisco J. Ortega, Josep M. Mercader, José Maria Moreno-Navarrete, Oscar Rovira, Ester Guerra, et al.. Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization. Diabetes Care, 2014, 37 (5), pp.1375-1383. ⟨10.2337/dc13-1847⟩. ⟨hal-01859430⟩
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