ArticleProceedings of the National Academy of Sciences of the United States of America2014
Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic β cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Proteostasis in the regulation of pancreatic islet cell plasticity.Journal of diabetes investigation · 2026Review
- Insulin receptor isoform B is required for efficient proinsulin processing in pancreatic β cells.iScience · 2024Article
- Autophagy Proteins and clinical data reveal the prognosis of polycystic ovary syndrome.BMC pregnancy and childbirth · 2024Article
- Top-Down Proteomics of Mouse Islets With Beta Cell CPE Deletion Reveals Molecular Details in Prohormone Processing.Endocrinology · 2023Article
- NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development.Nature communications · 2023Article
- Article
- Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice.Nature communications · 2022Article
- Mice heterozygous for a null mutation of CPE show reduced expression of carboxypeptidase e mRNA and enzyme activity but normal physiology, behavior, and levels of neuropeptides.Brain research · 2022Article
- Insulin Null β-cells Have a Prohormone Processing Defect That Is Not Reversed by AAV Rescue of Proinsulin Expression.Endocrinology · 2022Article
- Insulin regulates arginine-stimulated insulin secretion in humans.Metabolism: clinical and experimental · 2022Article
- Short Duration Alagebrium Chloride Therapy Prediabetes Does Not Inhibit Progression to Autoimmune Diabetes in an Experimental Model.Metabolites · 2021Article
- Article
- Translational Factor eIF4G1 Regulates Glucose Homeostasis and Pancreatic β-Cell Function.Diabetes · 2021Article
- Generalizing RNA velocity to transient cell states through dynamical modeling.Nature biotechnology · 2020Article
- Single-Cell RNA-Seq Reveals that CD9 Is a Negative Marker of Glucose-Responsive Pancreatic β-like Cells Derived from Human Pluripotent Stem Cells.Stem cell reports · 2020Article
- CD44, a Predominant Protein in Methylglyoxal-Induced Secretome of Muscle Cells, is Elevated in Diabetic Plasma.ACS omega · 2020Article
- Nutrient Sensor mTOR and OGT: Orchestrators of Organelle Homeostasis in PancreaticJournal of diabetes research · 2020Review
- Misfolded proinsulin impairs processing of precursor of insulin receptor and insulin signaling in β cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- eIF4G1 and carboxypeptidase E axis dysregulation inThe Journal of biological chemistry · 2019Article
- Metal-dependent hormone function: the emerging interdisciplinary field of metalloendocrinology.Metallomics : integrated biometal science · 2019Review
Corrections and comments
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Authors and funding
17 authors at 11 institutions in 2 countries.
Funding
Abstract
Insulin resistance, hyperinsulinemia, and hyperproinsulinemia occur early in the pathogenesis of type 2 diabetes (T2D). Elevated levels of proinsulin and proinsulin intermediates are markers of β-cell dysfunction and are strongly associated with development of T2D in humans. However, the mechanism(s) underlying β-cell dysfunction leading to hyperproinsulinemia is poorly understood. Here, we show that disruption of insulin receptor (IR) expression in β cells has a direct impact on the expression of the convertase enzyme carboxypeptidase E (CPE) by inhibition of the eukaryotic translation initiation factor 4 gamma 1 translation initiation complex scaffolding protein that is mediated by the key transcription factors pancreatic and duodenal homeobox 1 and sterol regulatory element-binding protein 1, together leading to poor proinsulin processing. Reexpression of IR or restoring CPE expression each independently reverses the phenotype. Our results reveal the identity of key players that establish a previously unknown link between insulin signaling, translation initiation, and proinsulin processing, and provide previously unidentified mechanistic insight into the development of hyperproinsulinemia in insulin-resistant states.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.