ArticlePloS one2013
Insulin therapy for pre-hyperglycemic beta-cell endoplasmic reticulum crowding.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Insulin gene mutations and posttranslational and translocation defects: associations with diabetes.Endocrine · 2020Pooled it
- Endoplasmic Reticulum Stress and Obesity.Advances in experimental medicine and biology · 2024Review
- Structural Lessons From the Mutant Proinsulin Syndrome.Frontiers in endocrinology · 2021Review
- Misfolded proinsulin in the endoplasmic reticulum during development of beta cell failure in diabetes.Annals of the New York Academy of Sciences · 2018Review
- Early Intensive Insulin Use May PreserveJournal of the Endocrine Society · 2018Article
- Diabetes associated with dominant insulin gene mutations: outcome of 24-month, sensor-augmented insulin pump treatment.Acta diabetologica · 2016Article
- Hyperglucagonemia in an animal model of insulin- deficient diabetes: what therapy can improve it?Clinical diabetes and endocrinology · 2016Article
- Diabetes mellitus due to the toxic misfolding of proinsulin variants.FEBS letters · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Insulin therapy improves β-cell function in early stages of diabetes by mechanisms that may exceed alleviation of glucotoxicity. In advance type 2 diabetes, hyperglycemia causes β-cell damage and ultimately β-cell loss. At such an advanced stage, therapeutic modalities are often inadequate. Growing evidence indicates that in early stages of type-2 diabetes and some types of monogenic diabetes linked with malfunctioning endoplasmic-reticulum (ER), the β-cell ER fails to process sufficient proinsulin once it becomes overloaded. These changes manifest with ER distention (ER-crowding) and deficiency of secretory granules. We hypothesize that insulin therapy may improves β-cell function by alleviating ER-crowding. To support this hypothesis, we investigated pre-diabetic β-cell changes in hProC(A7)Y-CpepGFP transgenic mice that develop prolonged pre-diabetes due to proinsulin dysmaturation and ER-crowding. We attenuated the β-cell ER proinsulin synthesis with a treat-to-target insulin therapy while avoiding hypoglycemia and weight gain. Alleviation of ER-crowding resulted in temporary improvement in proinsulin maturation, insulin secretion and glucose tolerance. Our observations suggest that alleviation of pre-diabetic ER-crowding using a treat-to-target insulin therapy may improve β-cell function and may prevent further metabolic deterioration.
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What OpenQuestion holds
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.