ESPE Yearbook of Paediatric Endocrinology

Brief Summary: Circulating microRNAs (miRNA) were measured using multiplatform sequencing in longitudinal samples from 262 individuals with newly diagnosed type 1 diabetes (T1D) enrolled in the INNODIA Natural History Study. A set of miRNAs located within the T1D susceptibility chromosomal locus 14q32 distinguished 2 groups of T1D: those with higher miRNA expression showed better glycemic outcomes and immunomics profile.MicroRNAs (miRNAs) are a class of ...

Brief Summary: This experimental study quantified the physiological contribution of pancreatic δ-cells to the glycemic set point. It used 3 orthogonal mouse models to remove somatostatin (SST) signalling within the pancreas or transplanted islets. Ablation of δ-cells or SST decreased the glycemic set point, and the glucose threshold for insulin response from β-cells, leading to increased insulin secretion to the same glucose challenge.The ...

Brief Summary: Through a series of experiments in the nonobese diabetic/Ltj mouse model and human β-cells, the authors show that the RANK pathway mediates cytokine-induced β-cell death through RANK-TRAF6 interaction and induction of NF-KB activation. Inhibition of the RANKL/RANK pathway following treatment with osteoprotegerin and denosumab protected β-cells against this cytotoxicity, reduced proinflammatory cytokines in activated T-cells, and reversed T1D in th...

Brief Summary: This experimental study unveiled a new link between the β-cell unfolded protein response and senescence. Deletion of the genes Atf6α or Ire1α in β-cells of non-obese diabetic (NOD) mice prior to insulitis generated a p21-driven early senescence phenotype, which altered the β-cell secretome and promoted protective M2 macrophages recruitment to pancreatic islets. M2 macrophages induced immune surveillance and removal of t...