Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells
Reads0
Chats0
TLDR
Pancreatic β cells are sensitive to excessive endoplasmic reticulum stress and dysregulated eIF2α phosphorylation, as indicated by transcriptome data, monogenic forms of diabetes and pharmacological studies, and should be taken into consideration when devising new therapeutic approaches for diabetes.Abstract:
Background
Pancreatic β cell dysfunction and death are central in the pathogenesis of most if not all forms of diabetes. Understanding the molecular mechanisms underlying β cell failure is important to develop β cell protective approaches.read more
Citations
More filters
Journal ArticleDOI
Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure.
TL;DR: New findings from studies performed on human β-cells or on samples obtained from patients with type 1 or type 2 diabetes mellitus are highlighted, focusing on studies performed at the β-cell level and the identification and characterization of the role of T1DM and T2DM candidate genes at theβ-celllevel.
Journal ArticleDOI
Recent Insights Into Mechanisms of β-Cell Lipo- and Glucolipotoxicity in Type 2 Diabetes.
TL;DR: The current evidence supporting the role of pancreatic β-cell lipo- and glucolipotoxicity in type 2 diabetes is reviewed, including lipid-based interventions in humans, prospective epidemiological studies and human genetic findings.
Journal ArticleDOI
Insulin mutations impair beta-cell development in a patient-derived iPSC model of neonatal diabetes
Diego Balboa,Jonna Saarimäki-Vire,Daniel Borshagovski,Mantas Survila,Päivi Lindholm,Emilia Galli,Solja Eurola,Jarkko Ustinov,Heli Grym,Hanna Huopio,Juha Partanen,Kirmo Wartiovaara,Kirmo Wartiovaara,Timo Otonkoski +13 more
TL;DR: It is shown that misfolded proinsulin impairs developingBeta-cell proliferation without increasing apoptosis, and neonatal diabetes-associated INS-mutations lead to defective beta-cell mass expansion, contributing to diabetes development.
Journal ArticleDOI
Regulation of autophagy by canonical and non-canonical ER stress responses.
TL;DR: Recent findings on the molecular mechanisms by which canonical and non-canonical ER stress responses can activate cytoprotective autophagy and contribute to tumor growth and therapy resistance are reviewed.
Calcium release channel RyR2 regulates insulin release and glucose homeostasis
Gaetano Santulli,Gennaro Pagano,Gennaro Pagano,Gennaro Pagano,Celestino Sardu,Celestino Sardu,Celestino Sardu,Wenjun Xie,Steven Reiken,Salvatore Luca D'Ascia,Michele Cannone,Nicola Marziliano,Bruno Trimarco,Theresa A. Guise,Alain Lacampagne,Andrew R. Marks +15 more
TL;DR: It is discovered that CPVT patients with mutant leaky RyR2 present with glucose intolerance, which was heretofore unappreciated, and the effects of the pharmacological inhibition of intracellular Ca2+ leak are verified.
References
More filters
Journal ArticleDOI
eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation
TL;DR: EIF5 stabilizes the binding of GDP to eIF2 and is therefore a bi-functional protein that acts as a GDP dissociation inhibitor (GDI) and a new step in the translation initiation pathway, one that is critical for normal translational controls.
Journal ArticleDOI
A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells
Pratik Saxena,Boon Chin Heng,Peng Bai,Marc Folcher,Henryk Zulewski,Henryk Zulewski,Martin Fussenegger,Martin Fussenegger +7 more
TL;DR: This designer network consisting of different network topologies orchestrating the timely control of transgenic and genomic Ngn3, Pdx1 and MafA variants is able to programme human induced pluripotent stem cells (hIPSCs)-derived pancreatic progenitor cells into glucose-sensitive insulin-secreting beta-like cells, whose glucose-stimulated insulin-release dynamics are comparable to human pancreatic islets.
Journal ArticleDOI
Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and beta cell development during the perinatal period.
Tsuyoshi Kayo,A Koizumi +1 more
TL;DR: Results suggest that Mody is involved in both islet growth and beta cell function, and specifically in the number of insulin secretory granules and a lower density of beta cells.
Journal ArticleDOI
Sulfonylureas Correct Trafficking Defects of ATP-sensitive Potassium Channels Caused by Mutations in the Sulfonylurea Receptor
Fei Fei Yan,Chia Wei Lin,Elizabeth Weisiger,Etienne A. Cartier,Grit Taschenberger,Show Ling Shyng +5 more
TL;DR: It is reported here that sulfonylureas also function as chemical chaperones to rescue KATP channel trafficking defects caused by two SUR1 mutations, A116P and V187D, identified in patients with congenital hyperinsulinism.
Journal ArticleDOI
Elevations in the Fasting Serum Proinsulin–to–C-Peptide Ratio Precede the Onset of Type 1 Diabetes
Emily K. Sims,Zunaira Chaudhry,Renecia A. Watkins,Farooq Syed,Janice S. Blum,Fangqian Ouyang,Susan M. Perkins,Raghavendra G. Mirmira,Jay M. Sosenko,Linda A. DiMeglio,Carmella Evans-Molina +10 more
TL;DR: The data suggest that β-cell ER dysfunction precedes type 1 diabetes onset, especially in younger children, and Elevations in the serum PI:C ratio may have utility in predicting the onset of type 1 Diabetes in the presymptomatic phase.