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

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... Full description

Journal Title: The journal of clinical endocrinology and metabolism 2014, Vol.99 (9), p.E1681-E1685
Main Author: Santovito, Donato
Other Authors: De Nardis, Velia , Marcantonio, Pamela , Mandolini, Claudia , Paganelli, Camilla , Vitale, Elita , Buttitta, Fiamma , Bucci, Marco , Mezzetti, Andrea , Consoli, Agostino , Cipollone, Francesco
Format: Electronic Article Electronic Article
Language: English
Subjects:
Abridged Index Medicus
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
Publisher: United States: Endocrine Society
ID: ISSN: 0021-972X
Link: https://www.ncbi.nlm.nih.gov/pubmed/24937531
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title: Plasma Exosome MicroRNA Profiling Unravels a New Potential Modulator of Adiponectin Pathway in Diabetes: Effect of Glycemic Control
format: Article
creator:
  • Santovito, Donato
  • De Nardis, Velia
  • Marcantonio, Pamela
  • Mandolini, Claudia
  • Paganelli, Camilla
  • Vitale, Elita
  • Buttitta, Fiamma
  • Bucci, Marco
  • Mezzetti, Andrea
  • Consoli, Agostino
  • Cipollone, Francesco
subjects:
  • Abridged Index Medicus
  • 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
ispartof: The journal of clinical endocrinology and metabolism, 2014, Vol.99 (9), p.E1681-E1685
description: 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.
language: eng
source:
identifier: ISSN: 0021-972X
fulltext: no_fulltext
issn:
  • 0021-972X
  • 1945-7197
url: Link


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titlePlasma Exosome MicroRNA Profiling Unravels a New Potential Modulator of Adiponectin Pathway in Diabetes: Effect of Glycemic Control
creatorSantovito, Donato ; De Nardis, Velia ; Marcantonio, Pamela ; Mandolini, Claudia ; Paganelli, Camilla ; Vitale, Elita ; Buttitta, Fiamma ; Bucci, Marco ; Mezzetti, Andrea ; Consoli, Agostino ; Cipollone, Francesco
creatorcontribSantovito, Donato ; De Nardis, Velia ; Marcantonio, Pamela ; Mandolini, Claudia ; Paganelli, Camilla ; Vitale, Elita ; Buttitta, Fiamma ; Bucci, Marco ; Mezzetti, Andrea ; Consoli, Agostino ; Cipollone, Francesco
descriptionContext: 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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subjectAbridged Index Medicus ; 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
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1De Nardis, Velia
2Marcantonio, Pamela
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5Vitale, Elita
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7Bucci, Marco
8Mezzetti, Andrea
9Consoli, Agostino
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0Plasma Exosome MicroRNA Profiling Unravels a New Potential Modulator of Adiponectin Pathway in Diabetes: Effect of Glycemic Control
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descriptionContext: 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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1Adiponectin - genetics
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4Case-Control Studies
5Diabetes Mellitus, Type 2 - drug therapy
6Diabetes Mellitus, Type 2 - genetics
7Diabetes Mellitus, Type 2 - metabolism
8Exosomes - genetics
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11Hyperglycemia - drug therapy
12Hyperglycemia - genetics
13Hyperglycemia - metabolism
14Hypoglycemic Agents - therapeutic use
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20Transcriptome
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titlePlasma Exosome MicroRNA Profiling Unravels a New Potential Modulator of Adiponectin Pathway in Diabetes: Effect of Glycemic Control
authorSantovito, Donato ; De Nardis, Velia ; Marcantonio, Pamela ; Mandolini, Claudia ; Paganelli, Camilla ; Vitale, Elita ; Buttitta, Fiamma ; Bucci, Marco ; Mezzetti, Andrea ; Consoli, Agostino ; Cipollone, Francesco
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7Diabetes Mellitus, Type 2 - metabolism
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12Hyperglycemia - genetics
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abstractContext: 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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pubEndocrine Society
pmid24937531
doi10.1210/jc.2013-3843
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