title: Plasma exosome microRNA profiling unravels a new potential modulator of adiponectin pathway in diabetes: effect of glycemic control.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This was a case-control study.
  
  
  METHODS
  Eighteen treatment-naïve diabetic patients with poor metabolic control and 12 control patients participated in the study.
  
  
  METHODS
  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.
authors.affiliation: Geriatric Clinic, European Center of Excellence on Atherosclerosis, Hypertension and Dyslipidemia, (D.S., V.D.N., P.M., C.M., C.P., E.V., M.B., A.M., F.C.) Clinical Research Center, Center of Excellence on Aging (D.S., V.D.N., P.M., C.M., C.P., M.B., A.M., A.C., F.C.), Center of Predictive Molecular Medicine, Center of Excellence on Aging (F.B.), Diabetes and Metabolism Unit, Department of Medicine and Aging Sciences (A.C.), "G. d'Annunzio" University, 66100 Chieti, Italy; and Institute for Cardiovascular Prevention (D.S.), Ludwig-Maximilians University, 80336 Munich, Germany.
authors.forename: Donato
authors.initials: D
authors.lastname: Santovito
authors.forename: Velia
authors.initials: V
authors.lastname: De Nardis
authors.forename: Pamela
authors.initials: P
authors.lastname: Marcantonio
authors.forename: Claudia
authors.initials: C
authors.lastname: Mandolini
authors.forename: Camilla
authors.initials: C
authors.lastname: Paganelli
authors.forename: Elita
authors.initials: E
authors.lastname: Vitale
authors.forename: Fiamma
authors.initials: F
authors.lastname: Buttitta
authors.forename: Marco
authors.initials: M
authors.lastname: Bucci
authors.forename: Andrea
authors.initials: A
authors.lastname: Mezzetti
authors.forename: Agostino
authors.initials: A
authors.lastname: Consoli
authors.forename: Francesco
authors.initials: F
authors.lastname: Cipollone
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D055354:Exosomes / Q000235:genetics*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D059467:Transcriptome
chemical_list: D052242:Adiponectin; D007004:Hypoglycemic Agents; D035683:MicroRNAs