Plasma Exosome MicroRNA Profiling Unravels a New Potential Modulator of Adiponectin Pathway in Diabetes: Effect of Glycemic Control

• Published in: The journal of clinical endocrinology and metabolism 2014-09, Vol.99 (9), p.E1681-E1685
• Main Authors: Santovito, Donato, De Nardis, Velia, Marcantonio, Pamela, Mandolini, Claudia, Paganelli, Camilla, Vitale, Elita, Buttitta, Fiamma, Bucci, Marco, Mezzetti, Andrea, Consoli, Agostino, Cipollone, Francesco
• Format: Article
• Language: English
• Subjects: Adiponectin - genetics; Adiponectin - metabolism; Aged; Case-Control Studies; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Exosomes - genetics; Female; Humans; Hyperglycemia - drug therapy; Hyperglycemia - genetics; Hyperglycemia - metabolism; Hypoglycemic Agents - therapeutic use; Insulin Resistance - genetics; Male; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; Transcriptome
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2013-3843

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.