Endocrine Abstracts

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...

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...

MicroRNAs (miRNAs) are small non-coding RNAs that repress protein production post-transcriptionally. MiRNAs play crucial roles in metabolism, endocrine cells development and in processes altered in T2D, such as insulin secretion. MiR-125b controls proliferation, apoptosis and differentiation of various cell types, although its role in β-cells remains unclear. Recent studies show an association between high levels of circulating miR-125b and hyperglycaemia (HbA1c) in predi...

Introduction: Pancreatic β-cells control glucose homeostasis by secreting insulin in response to high glucose. MiRNAs regulate β-cell function and contribute to β-cell failure in type 2 diabetes. MiR-184 regulates β-cell compensatory expansion during pregnancy and obesity and its expression is reduced by glucose through unknown mechanisms. AMPK is a suggested target of antidiabetic drugs and an important energy sensor. Its β-cell-selective inactivation...

Subpopulations of beta cells dictate overall ‘pacing’ of insulin secretion across the islet and therefore the control of glycaemia. Functional beta cell subpopulations also exist in human islets and have an altered subtype distribution in type 2 diabetes. However, the molecular control of the establishment and maintenance of beta cell hierarchy is poorly understood. We hypothesised that the epigenome would govern this heterogeneity. We have identified a novel subpopu...

Background: Limited data exists on the hormonal mediators connecting metabolism and reproduction. Animal studies show that the reproductive hormone, kisspeptin, may also be important in metabolism. We investigated the effects of kisspeptin on human metabolism for the first time, to explore possible kisspeptin-mediated links between reproduction and metabolism.Methods: We performed intravenous glucose tolerance tests (IVGTTs) in 15 healthy men (age 25&#17...

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 ...