Endocrine Abstracts

Background and aim: Loss-of-function mutations in TRMT10A, a transfer RNA (tRNA) methyltransferase, cause early onset diabetes and microcephaly. tRNAs play a crucial role in cellular homeostasis and post-transcriptional modifications modulate tRNA function and fragmentation. tRNA-derived halves (tiRNAs, 29-50 nt) and fragments (tRFs, 14-30 nt) are a new class of functional small noncoding RNAs, involved in cellular stress responses. Here we set out to investigate the ...

Aim of the work: Diabetes is characterized by progressive loss of functional pancreatic beta cells. None of the therapeutic agents used to treat diabetes arrest this process and preventing beta cell loss remains a major unmet need. We have previously shown that serum from 8 young healthy males who exercised for 8 weeks protects human islets and human insulin-producing EndoC-βH1 cells from apoptosis induced by pro-inflammatory cytokines or the endoplasmic reticulum (ER) st...

Aim: IFNα is a key regulator of the initial dialogue between pancreatic β-cells and the immune system in type 1 diabetes (T1D). IFNα induces endoplasmic reticulum (ER) stress, insulitis and a massive HLA-ABC overexpression in human β-cells, three histological hallmarks of T1D. Against this background we investigated the global role of IFNα on iPSC-derived islet-like cells, used here to mimic islet cells in the early neonatal period when autoimmunity ag...

Objective: Neonatal diabetes is caused by single gene mutations reducing pancreatic β-cell number or impairing β-cell function. Understanding the genetic underpinnings of rare diabetes subtypes highlights fundamental biological processes in β-cells. Our aim was to explore the genetic basis of a syndrome characterized by neonatal diabetes, microcephaly and epilepsy.Methods: We performed whole genome sequencing for 2 unrelated patients with ...