On the Immense Variety and Complexity of Circumstances Conditioning Pancreatic β-Cell Apoptosis in Type 1 Diabetes
- 1Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
- 2Diabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy
- 3Umberto Di Mario ONLUS Research Foundation, Toscana Life Science Park, Siena, Italy
- Corresponding author: Decio L. Eizirik, .
In his masterpiece War and Peace (1869), Leo Tolstoy wrote: “The human intellect with no inkling of the immense variety and complexity of circumstances conditioning a phenomenon, any one of which may be separately conceived as the cause of it, snatches at the first and the most easily understood approximation, and says: ‘Oh, here is the cause!’” The field of type 1 diabetes has been plagued by this trend for oversimplification. As a result, individual pathways are often suggested as “the cause” of this complex, multifactorial, and probably heterogeneous disease, thereby leading to therapeutic attempts that nearly always end in failure.
MicroRNAs (miRNAs) are a family of endogenous single-stranded RNA molecules around 22 nucleotides in length (1). They are highly conserved among species and regulate the expression of partially complementary protein-coding genes by either degrading or preventing translation of target messenger RNAs. miRNAs are transcribed from individual genes, located in exons or introns of protein-coding genes or in intergenic regions, and are often clustered (2). Importantly, >50% of human genes may be at least in part regulated by miRNAs (3), adding an extra level of regulation for gene expression. An article by Roggli et al. (4) published in this issue of Diabetes describes a microarray analysis on islets obtained from 4- and 8-week-old female NOD mice (an animal model of autoimmune diabetes, in which 4-week-old animals have little or no immune infiltration whereas 8-week-old mice show insulitis in most islets; hyperglycemia usually starts after 14 weeks of age). They observed a preferential increase in miR-29a/b/c in the islets obtained from 8-week-old animals, a finding confirmed by other methods in …