ReviewDiabetes2021
Possible Involvement of Adipose Tissue in Patients With Older Age, Obesity, and Diabetes With SARS-CoV-2 Infection (COVID-19) via GRP78 (BIP/HSPA5): Significance of Hyperinsulinemia Management in COVID-19.
Review in Diabetes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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, 2 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- A Systematic Review of Proteomics in Obesity: Unpacking the Molecular Puzzle.Current obesity reports · 2024Pooled it
- Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review.Molecular medicine (Cambridge, Mass.) · 2023Pooled it
- Homoharringtonine exhibits senotherapeutic activity that mitigates diet- and age-associated obesity and insulin resistance and extends lifespan in mice.Nature communications · 2026Article
- The Role of Crosstalk Between the Unfolded Protein Response and Autophagy in Diseases Associated with Sympathetic Nervous System Imbalance: Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- GRP78 in human diseases: From molecular chaperone to therapeutic target.Theranostics · 2026Review
- From zoonotic spillover to endemicity: the broad determinants of human coronavirus tropism.mBio · 2025Review
- Article
- Unraveling the mechanisms underlying diabetic cataracts: insights from Mendelian randomization analysis.Redox report : communications in free radical research · 2024Article
- Rising tide: The global surge of type 2 diabetes in children and adolescents demands action now.World journal of diabetes · 2024Article
- Diabetes Mellitus, Energy Metabolism, and COVID-19.Endocrine reviews · 2024Review
- Article
- COVID-19, Obesity, and GRP78: Unraveling the Pathological Link.Journal of obesity & metabolic syndrome · 2023Review
- Effect of temperature and nucleotide on the binding of BiP chaperone to a protein substrate.Protein science : a publication of the Protein Society · 2023Article
- Oxygen Requirement in Overweight/Obese Kidney Transplant Recipients with COVID-19: An Observational Cohort Study.Diagnostics (Basel, Switzerland) · 2023Article
- Review
- Identification of immune-related genes and patient selection for hepatocellular carcinoma immunotherapy.Translational cancer research · 2023Article
- GRP78 Inhibitor YUM70 Suppresses SARS-CoV-2 Viral Entry, Spike Protein Production and Ameliorates Lung Damage.Viruses · 2023Article
- Association of Serum Vaspin Concentration with Metabolic Disorders in Obese Individuals.Biomolecules · 2023Article
- Potential of green tea EGCG in neutralizing SARS-CoV-2 Omicron variant with greater tropism toward the upper respiratory tract.Trends in food science & technology · 2023Review
- New progresses on cell surface protein HSPA5/BiP/GRP78 in cancers and COVID-19.Frontiers in immunology · 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
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging, obesity, and diabetes are major risk factors for the severe progression and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]), but the underlying mechanism is not yet fully understood. In this study, we found that the SARS-CoV-2 spike protein physically interacts with cell surface GRP78, which promotes the binding to and accumulation in ACE2-expressing cells. GRP78 was highly expressed in adipose tissue and increased in humans and mice with older age, obesity, and diabetes. The overexpression of GRP78 was attributed to hyperinsulinemia in adipocytes, which was in part mediated by the stress-responsive transcription factor XBP-1s. Management of hyperinsulinemia by pharmacological approaches, including metformin, sodium-glucose cotransporter 2 inhibitor, or β3-adrenergic receptor agonist, decreased GRP78 gene expression in adipose tissue. Environmental interventions, including exercise, calorie restriction, fasting, or cold exposure, reduced the gene expression of GRP78 in adipose tissue. This study provides scientific evidence for the role of GRP78 as a binding partner of the SARS-CoV-2 spike protein and ACE2, which might be related to the severe progression and outcome of COVID-19 in patients with older age, obesity, and diabetes. The management of hyperinsulinemia and the related GRP78 expression could be a therapeutic or preventative target.
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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.