Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes
Résumé
Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians-an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.
Mots clés
Diabetes Mellitus
Experimental/blood/genetics/pathology
Female
Humans
Male
Biomarkers/blood
Animals
Mice
Inbred C57BL
Insulin Resistance
Insulin/blood
Middle Aged
Cholesterol/blood
Blood Glucose/metabolism
Gene Expression Regulation
Adult
Type 2/*blood/ethnology/genetics/pathology
Ethnic Groups
Prediabetic State/*blood/ethnology/genetics/pathology
MicroRNAs/*blood/genetics
Glucose Intolerance
Fasting
*Phenotype
Glycosylated/metabolism
Hemoglobin A
Glucose Tolerance Test
Case-Control Studies
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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