We discuss current knowledge about microRNAs (miRNAs) in type 1 diabetes (T1D), an autoimmune disease leading to severe loss of pancreatic β-cells. We describe: the role of cellular miRNAs in regulating immune functions and pathways impacting insulin secretion and β-cell survival; circulating miRNAs as disease biomarkers.
Studies examined miRNAs in experimental models and patients, including analysis of tissues from organ donors, peripheral blood cells, and circulating miRNAs in serum, plasma, and exosomes. Studies employed diverse designs and methodologies to detect miRNAs and measure their levels. Selected miRNAs have been linked to the regulation of key biological pathways and disease pathogenesis; several circulating miRNAs are associated with having T1D, islet autoimmunity, disease progression, and immune and metabolic functions, for example, C-peptide secretion, in multiple studies.
A growing literature reveals multiple roles of miRNAs in T1D, provide new clues into the regulation of disease mechanisms, and identify reproducible associations. Yet challenges remain, and the field will benefit from joint efforts to analyze results, compare methodologies, formally test the robustness of miRNA associations, and ultimately move towards validating robust miRNA biomarkers.
aDiabetes Unit, Department of Medicine, Surgery and Neuroscience, University of Siena
bFondazione Umberto di Mario, Toscana Life Sciences, Siena, Italy
cDiabetes Research Institute
dDepartment of Medicine, Division of Endocrinology and Metabolism
eDepartment of Microbiology and Immunology, Leonard Miller School of Medicine, University of Miami, Miami, Florida, USA
Correspondence to Francesco Dotta, MD, Diabetes Unit, Department of Medicine, Surgery and Neuroscience, University of Siena and Fondazione Umberto di Mario, Toscana Life Sciences, Viale Bracci 18, 53100 Siena, Italy. Tel: +39 577 586269; fax: +39 577 586186; e-mail: firstname.lastname@example.org