Searchable abstracts of presentations at key conferences in endocrinology

ea0057001 | tRNAGln hypomethylation and fragmentation in patient iPSC-derived β-like cells mediates apoptosis in TRMT10A diabetes | BES2018

tRNAGln hypomethylation and fragmentation in patient iPSC-derived β-like cells mediates apoptosis in TRMT10A diabetes

Cristina Cosentino , Sanna Toivonen , Stephane Demine , Andrea Schiavo , Nathalie Pachera , Decio L Eizirik , Miriam Cnop , Mariana Igoillo-Esteve

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 ...

ea0057003 | Use of 3D culture systems to generate human induced pluripotent stem cell-derived β-cells in vitro | BES2018

Use of 3D culture systems to generate human induced pluripotent stem cell-derived β-cells in vitro

Federica Fantuzzi , Sanna Toivonen , Alex Schiavo Andrea , Nathalie Pachera , Bahareh Rajaei , Ying Cai , Mariana Igoillo-Esteve , Eizirik Decio L , Miriam Cnop

Background and aims: Diabetes currently affects 425 million people worldwide. Pancreatic β-cell failure is central in the development and progression of type 1 and type 2 diabetes. Diabetes research is slowed by the difficulty to study the diseased tissue, i.e. human islet bcells: these are only available in a few donor organ transplantation centers worldwide. β-cells differentiated from human induced pluripotent stem cells (hiPSCs) represent a novel cell source. Cur...

ea0057004 | GLP-1 analogs protect beta cells and prevent diabetes in models of Wolfram syndrome | BES2018

GLP-1 analogs protect beta cells and prevent diabetes in models of Wolfram syndrome

Mariana Igoillo-Esteve , Sanna Toivonen , Paraskevi Salpea , Cristina Cosentino , Bahareh Rajaei , Anyishai Musuaya , Nathalie Pachera , Piero Marchetti , Cris Brown , Fumihiko Urano , Eizirik Decio L , Miriam Cnop

Background and aims: Wolfram syndrome is a rare autosomal recessive orphan disease. The clinical manifestations are young onset diabetes, optic nerve atrophy and deafness. Most Wolfram patients carry mutations in WFS1. WFS1 deficiency results in endoplasmic reticulum (ER) stress, leading to neurodegeneration and pancreatic β-cell dysfunction and death. Glucagon-like peptide-1 (GLP-1) analogs and the cAMP inducer forskolin have been shown to protect β-cells f...

ea0088004 | Abstracts | BES2022

Understanding pathogenic mechanisms and identifying therapeutic avenues in MEHMO syndrome using patient’s induced pluripotent stem cells

Hadis Shakeri , Izzet Mehmet Akcay , Mayank Bansal , Ying Cai , Chiara Vinci , Nathalie Pachera , Hanne Willems , Federica Fantuzzi , Yue Tong , Daniela Gasperikova , Miriam Cnop

Background and aims: MEHMO is an X-linked syndrome comprising Mental retardation, Epilepsy, Hypogenitalism, Microcephaly and Obesity. It is caused by a damaging p.Ile465Serfs frameshift mutation in EIF2S3 that encodes the □ subunit of eukaryotic translation initiation factor 2 (eIF2), essential for protein synthesis and regulation of the integrated stress response. Patients with this EIF2S3 mutation also have neonatal hypoglycemia, early onset insulin-...