miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes.
Background. The use of miRNAs as biomarkers for Type 1 Diabetes (T1D) risk is attractive as T1D is usually diagnosed in front of acute symptoms. As miR-375 is highly expressed in the endocrine pancreas, we postulated that its circulating level might reflect beta cell alterations and might be altered in the blood of T1D patients recently diagnosed. Methods. Sera were obtained from 22 T1D children at onset of the disease, before subcutaneous insulin treatment, and from 10 nondiabetic pediatric controls. MiR-375 seric level was quantified by stem-loop RT-PCR-based assay. MiRNAs regulations in isolated human islets in response to high glucose concentrations were determined by TaqMan Low-Density Array. Results. The abundance of miR-375, among the 410 miRNAs detected in human islets, mirrored its well-established role in rodent islet biology. Upregulated miRNAs targeted genes involved in islet homeostasis and regulation of beta cell mass. Downregulated miRNAs, including miR-375, were involved in pancreas secretion and protein turnover. Seric level of miR-375 was lower in T1D children versus age-matched controls, without any correlations with HbA1c, glycaemia, and number of autoantibodies. Conclusion. Altered circulating level of miR-375 at onset of T1D might be a general biomarker of metabolic alterations and inflammation associated with the disease.
CarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, France; Hospices Civils de Lyon, Lyon-Sud Hospital, Department of Diabetology and Endocrinology, 69495 Pierre-Bénite, France.
Lucien
L
Marchand
CarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, France.
Audrey
A
Jalabert
CarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, France.
Emmanuelle
E
Meugnier
Hospices Civils de Lyon, Department of Pediatric Endocrinology, Femme-Mère-Enfant Hospital, 69500 Bron, France.
Kathleen
K
Van den Hende
Hospices Civils de Lyon, INSERM U851, Lyon-Sud Hospital, Department of Immunology, 69495 Pierre-Bénite, France.
Nicole
N
Fabien
CarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, France; Hospices Civils de Lyon, Department of Pediatric Endocrinology, Femme-Mère-Enfant Hospital, 69500 Bron, France.
Marc
M
Nicolino
CarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, France.
Anne-Marie
AM
Madec
CarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, France; Hospices Civils de Lyon, Lyon-Sud Hospital, Department of Diabetology and Endocrinology, 69495 Pierre-Bénite, France.
Charles
C
Thivolet
CarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, France.
Sophie
S
Rome
D000293:Adolescent; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000097:blood*
C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D005947:Glucose