, Volume 60, Issue 8, pp 1361–1362 | Cite as

Up front

Up front

Beta cell heterogeneity: an evolving concept

Dana Avrahami, Agnes Klochendler, Yuval Dor, Benjamin Glaser

It is well known that beta cells are functionally heterogeneous, but the significance of this in health and disease is not known. Studies using emerging technologies are now addressing this question. In this issue, Avrahami et al (DOI  10.1007/s00125-017-4326-z) provide a concise overview of the impact of novel technologies on our understanding of the emerging field of beta cell heterogeneity. At the whole-islet level, a functional control network was discovered that coordinates insulin secretion within the islet. On the single-cell level, cell surface markers, transcriptomics and proteomics can classify beta cells into different groups and demonstrate that the relative size of these groups changes with age and disease. Single-cell technologies provide information on rare cell types, such as proliferating islet cells. While many questions remain unanswered, it is clear that with these novel technologies we are at the brink of a new era in our understanding of islet cell function.

Early prediction of autoimmune (type 1) diabetes

Simon E. Regnell, Åke Lernmark

Prospective studies from birth of children at increased genetic risk for autoimmune (type 1) diabetes have provided novel insights into the aetiology and pathogenesis of this disease. In this issue, Regnell and Lernmark (DOI  10.1007/s00125-017-4308-1) summarise recent advances that suggest it should eventually be possible to dissect fully the autoimmune reaction against islet beta cells. Genes in the HLA-DR-DQ region on chromosome 6 seem to play a role in the response to a hypothetical environmental insult. One such insult might result in the appearance of insulin autoantibodies with an incidence peak at 1–3 years of age, primarily in children with the DR4-DQ8 haplotype. Another insult might occur later, reaching a plateau of GAD autoantibodies at about 3 years of age, primarily in children with the DR3-DQ2 haplotype. The subsequent pathogenesis seems to be related to a non-HLA-related appearance of a second, third or fourth islet autoantibody, resulting in a variable rate of progression to beta cell loss and clinical onset. Staging pathogenesis should prove useful in dissecting the specific mechanisms of beta cell destruction with a view to achieving secondary prevention of type 1 diabetes.

Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes

Isaac V. Snowhite, Gloria Allende, Jay Sosenko, Ricardo L. Pastori, Shari Messinger Cayetano, Alberto Pugliese

Screening for autoantibodies against islet cell autoantigens identifies individuals at risk of type 1 diabetes; yet, progression to overt disease is heterogeneous and additional biomarkers could improve prediction and risk stratification for prevention trials. In this issue, Snowhite et al (DOI  10.1007/s00125-017-4294-3) identify circulating microRNAs associated with disease progression in autoantibody-positive children and adolescents participating in the TrialNet Pathway to Prevention Study. Increased levels of these microRNAs were associated with higher risk of disease progression and correlated with measures of impaired insulin secretion assessed during an OGTT. Several of these microRNAs play a role in beta cell function and insulin secretion, and some may be induced by viruses. Replication in additional longitudinal cohorts may validate these microRNAs as novel biomarkers and functional studies may reveal mechanisms of beta cell dysfunction during the development of type 1 diabetes.

HSF1 acetylation decreases its transcriptional activity and enhances glucolipotoxicity-induced apoptosis in rat and human beta cells

Indri Purwana, Jun J. Liu, Bernard Portha, Jean Buteau

Diabetes is characterised by a progressive deterioration of beta cell mass and function. However, the precise mechanisms underlying beta cell loss remain elusive. In this issue, Purwana et al (DOI  10.1007/s00125-017-4310-7) report that metabolic stress induces acetylation and inhibition of the transcription factor heat shock factor protein 1 (HSF1) in beta cells, thereby causing apoptosis. Conversely, restoration of HSF1 activity alleviates stress and promotes beta cell survival. The authors also demonstrate that expression of HSF1 and its target genes are altered in islets from diabetic Goto–Kakizaki rats, a well characterised model of spontaneous type 2 diabetes. These findings unveil a critical role for HSF1 in the regulation of beta cell survival and support the therapeutic potential of HSF1-targeting agents in diabetes treatment.

All text supplied by the authors.

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© Springer-Verlag GmbH Germany 2017

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