ArticleProceedings of the National Academy of Sciences of the United States of America2019
Sustained ER stress promotes hyperglycemia by increasing glucagon action through the deubiquitinating enzyme USP14.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
36 citing papers in PubMed, 57 citations in OpenAlex.
- Hepatic PDIA5 improves hyperglycaemia and insulin resistance through stabilisation of ATF6.Diabetologia · 2026Article
- MAPK Phosphatase-3 Mediates Chronic Endoplasmic Reticulum Stress Promoting Hepatic Gluconeogenesis.International journal of molecular sciences · 2026Article
- Ubiquitination modifications as central regulators of metabolic dysfunction in type 2 diabetes mellitus.Frontiers in endocrinology · 2026Review
- Hyperglycemia in combination with excess fat intake promotes renal pyroptosis and fibrosis through GαTheranostics · 2026Article
- The beneficial effect of hepatic ER stress-associated protein PDI on obesity-associated glucose dysregulation.Nutrition & metabolism · 2025Article
- Molecular and biological approach to ischemia/reperfusion in diabetes conditions.Molecular biology reports · 2025Review
- Bromocriptine improves glucose tolerance in obese mice via central dopamine D2 receptor-independent mechanism.PloS one · 2025Article
- Relevant Serum Endoplasmic Reticulum Stress Biomarkers in Type 2 Diabetes and Its Complications: A Systematic Review and Meta-Analysis.Antioxidants (Basel, Switzerland) · 2024Review
- Palmitic acid promotes miRNA release from adipocyte exosomes by activating NF-κB/ER stress.Nutrition & diabetes · 2024Article
- Heat Shock Response and Heat Shock Proteins: Current Understanding and Future Opportunities in Human Diseases.International journal of molecular sciences · 2024Review
- Integration of dietary nutrition and TRIB3 action into diabetes mellitus.Nutrition reviews · 2024Review
- Identification of common genes and pathways between type 2 diabetes and COVID-19.Frontiers in genetics · 2024Article
- Roles of ubiquitin-specific proteases in inflammatory diseases.Frontiers in immunology · 2024Review
- miR-26a-5p Attenuates Oxidative Stress and Inflammation in Diabetic Retinopathy through the USP14/NF-Journal of ophthalmology · 2024Article
- USP14 Regulates ATF2/PIK3CD Axis to Promote Microvascular Endothelial Cell Proliferation, Migration, and Angiogenesis in Diabetic Retinopathy.Biochemical genetics · 2023Article
- USP14 governs CYP2E1 to promote nonalcoholic fatty liver disease through deubiquitination and stabilization of HSP90AA1.Cell death & disease · 2023Article
- Activation of insulin-like growth factor-1 receptor (IGF-1R) promotes growth of colorectal cancer through triggering the MEX3A-mediated degradation of RIG-I.Acta pharmaceutica Sinica. B · 2023Article
- Low-Protein Diets Composed of Protein Recovered from Food Processing Supported Growth, but Induced Mild Hepatic Steatosis Compared with a No-Protein Diet in Young Female Rats.The Journal of nutrition · 2023Article
- Cerebral Glucose Metabolism and Potential Effects on Endoplasmic Reticulum Stress in Stroke.Aging and disease · 2023Review
- Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress plays an important role in metabolic diseases like obesity and type 2 diabetes mellitus (T2DM), although the underlying mechanisms and regulatory pathways remain to be elucidated. Here, we induced chronic low-grade ER stress in lean mice to levels similar to those in high-fat diet (HFD)-fed obese mice and found that it promoted hyperglycemia due to enhanced hepatic gluconeogenesis. Mechanistically, sustained ER stress up-regulated the deubiquitinating enzyme ubiquitin-specific peptidase 14 (USP14), which increased the stability and levels of 3',5'-cyclic monophosphate-responsive element binding (CREB) protein (CBP) to enhance glucagon action and hepatic gluconeogenesis. Exogenous overexpression of USP14 in the liver significantly increased hepatic glucose output. Consistent with this, liver-specific knockdown of USP14 abrogated the effects of ER stress on glucose metabolism, and also improved hyperglycemia and glucose intolerance in obese mice. In conclusion, our findings show a mechanism underlying ER stress-induced disruption of glucose homeostasis, and present USP14 as a potential therapeutic target against T2DM.
Indexed as
Identifiers
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.