Plasma exosome microRNA profiling unravels a new potential modulator of adiponectin pathway in diabetes: effect of glycemic control

D Santovito, V De Nardis, P Marcantonio… - The Journal of …, 2014 - academic.oup.com
D Santovito, V De Nardis, P Marcantonio, C Mandolini, C Paganelli, E Vitale, F Buttitta…
The Journal of Clinical Endocrinology & Metabolism, 2014academic.oup.com
Context: Type 2 diabetes is a chronic disease characterized by inadequate β-cell response
to the progressive insulin resistance. MicroRNAs (miRNAs) are short, endogenous,
noncoding RNAs representing a class of powerful gene expression modulators. Previous
population studies observed a modulation of circulating miRNAs in diabetic patients;
however, few data are presently available on miRNA modulation in diabetic patients naïve to
pharmacological treatment as well as the effect of glycemic control on this. Objective: We …
Context
Type 2 diabetes is a chronic disease characterized by inadequate β-cell response to the progressive insulin resistance. MicroRNAs (miRNAs) are short, endogenous, noncoding RNAs representing a class of powerful gene expression modulators. Previous population studies observed a modulation of circulating miRNAs in diabetic patients; however, few data are presently available on miRNA modulation in diabetic patients naïve to pharmacological treatment as well as the effect of glycemic control on this.
Objective
We aimed at studying circulating miRNA expression in diabetic patients naïve to treatment and at investigating the influence on this of glycemic control.
Design
This was a case-control study.
Participants
Eighteen treatment-naïve diabetic patients with poor metabolic control and 12 control patients participated in the study.
Main Outcome Measures
Wide miRNA expression profiling was performed, and the expression of miRNAs found to be dysregulated was then validated by quantitative RT-PCR. Finally, algorithm-identified putative miRNA targets were evaluated by quantitative RT-PCR and ELISA.
Results
In diabetic patients, microarray analysis showed that four miRNAs are increased, whereas 21 miRNAs are decreased. Quantitative RT-PCR validation confirmed the significant up-regulation of miR-326 (P = .004) and down-regulation of let-7a (P < .001) and let-7f (P = .003). Notably, an inverse negative correlation was found between circulating miR-326 and its putative target adiponectin (p = −0.479, P = .009). After 12 months of antidiabetic treatment, quantitative RT-PCR data analysis showed that miR-326 levels were unaffected, whereas the levels of let-7a and let-7f were significantly increased.
Conclusions
Treatment-naïve, poorly controlled diabetic patients show a significant dysregulation of miRNAs involved in the regulation of the adiponectin pathway, a phenomenon that may be reversed, at least in part, by improved glycemic control.
Oxford University Press