Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells
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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
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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.
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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.
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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.
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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
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Journal ArticleDOI
Early insulin therapy prevents beta cell loss in a mouse model for permanent neonatal diabetes (Munich Ins2 C95S)
TL;DR: It is concluded that early insulin treatment protects Munich Ins2C95S mutant mice from insulin resistance, alpha cell hyperfunction, beta cell loss and hyperplasia of non-beta cells, some well-known features of human diabetes mellitus.
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Integration-Free Human Induced Pluripotent Stem Cells From Type 1 Diabetes Patient Skin Fibroblasts Show Increased Abundance of Pancreas-Specific microRNAs.
Jun Liu,Mugdha V. Joglekar,Huseyin Sumer,Anandwardhan A. Hardikar,Helena J. Teede,Paul J. Verma +5 more
TL;DR: Data indicate that T1D patient skin fibroblasts can be reprogrammed to pluripotency using a synthetic mRNA approach and can serve as a useful tool for the identification of genes that are involved in autoimmune reactions as well as generating patient-matched β-cells for cell-based therapy.
Maintenance of Pdx1 mRNA translation in islet β-cells during the unfolded protein response
TL;DR: These findings suggest that Pdx1 protein levels are maintained in the setting of the UPR, in part, through elements in the 5'-untranslated region that confer privileged mRNA translation in a 5'-7-methylguanylate cap-independent manner.
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Common variants in PERK, JNK, BIP and XBP1 genes are associated with the risk of prediabetes or diabetes-related phenotypes in a Chinese population.
Nan Feng,Xiaowei Ma,Xiaowei Wei,Junqing Zhang,Aimei Dong,Mengmeng Jin,Hong Zhang,Xiaohui Guo +7 more
TL;DR: Common variants at PERK and BIP loci contributed to the risk of prediabetes, and the genetic variations in JNK and XBP1 genes are associated with diabetes-related clinical parameters in this Chinese population.
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Infantile Cirrhosis, Growth Impairment, and Neurodevelopmental Anomalies Associated with Deficiency of PPP1R15B
Saeed Mohammad,Lynne A. Wolfe,Petra Stöbe,Saskia Biskup,Mark S. Wainwright,Hector Melin-Aldana,Padmini Malladi,Maximilian Muenke,William A. Gahl,Peter F. Whitington +9 more
TL;DR: The first demonstration of P PP1R15B associated with liver disease expands the phenotypic spectrum of PPP1R 15B related diseases and validate the application of WES in the diagnosis of children with undetermined liver disease.