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  • Title: Plasma exosome microRNA profiling unravels a new potential modulator of adiponectin pathway in diabetes: effect of glycemic control.
    Author: Santovito D, De Nardis V, Marcantonio P, Mandolini C, Paganelli C, Vitale E, Buttitta F, Bucci M, Mezzetti A, Consoli A, Cipollone F.
    Journal: J Clin Endocrinol Metab; 2014 Sep; 99(9):E1681-5. PubMed ID: 24937531.
    Abstract:
    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.
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