ArticleDiabetes2014
Insulin regulates the unfolded protein response in human adipose tissue.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 37 citations in OpenAlex.
- The unfolded protein response and its activation by insulin in muscle are not altered by obesity or type 2 diabetes.Clinical science (London, England : 1979) · 2026Article
- Succinylation modification in diabetes and diabetic complications: Mechanisms and functions (Review).Molecular medicine reports · 2026Review
- Adipose tissue dysfunction disrupts metabolic homeostasis: mechanisms linking fat dysregulation to disease.Frontiers in endocrinology · 2025Review
- Review
- Insulin and aging - a disappointing relationship.Frontiers in endocrinology · 2023Review
- Impaired insulin signalling and allostatic load in Alzheimer disease.Nature reviews. Neuroscience · 2022Review
- Guenther Boden, MD (1935-2015): A Pioneer in Human Studies of Nutrition and Obesity-And the Mystery of Insulin Resistance for Handling Glucose.Diabetes care · 2020Article
- Endoplasmic reticulum stress causes insulin resistance by inhibiting delivery of newly synthesized insulin receptors to the cell surface.Molecular biology of the cell · 2020Article
- Insulin: too much of a good thing is bad.BMC medicine · 2020Review
- Fumarate and oxidative stress synergize to promote stability of C/EBP homologous protein in the adipocyte.Free radical biology & medicine · 2020Article
- Succination of Protein Disulfide Isomerase Links Mitochondrial Stress and Endoplasmic Reticulum Stress in the Adipocyte During Diabetes.Antioxidants & redox signaling · 2017Article
- Is the calorie concept a real solution to the obesity epidemic?Global health action · 2017Article
- Role of endoplasmic reticulum stress signalling in diabetic endothelial dysfunction and atherosclerosis.Diabetes & vascular disease research · 2017Review
- Hyperactivation of the Insulin Signaling Pathway Improves Intracellular Proteostasis by Coordinately Up-regulating the Proteostatic Machinery in Adipocytes.The Journal of biological chemistry · 2016Article
- Endoplasmic reticulum proteostasis in hepatic steatosis.Nature reviews. Endocrinology · 2016Review
- Insulin Protects Hepatic Lipotoxicity by Regulating ER Stress through the PI3K/Akt/p53 Involved Pathway Independently of Autophagy Inhibition.Nutrients · 2016Article
- The effect of glucose concentration and sodium phenylbutyrate treatment on mitochondrial bioenergetics and ER stress in 3T3-L1 adipocytes.Biochimica et biophysica acta · 2015Article
- Decreased secretion of adiponectin through its intracellular accumulation in adipose tissue during tobacco smoke exposure.Nutrition & metabolism · 2015Article
- Article
- Response to comment on Boden et al. Insulin regulates the unfolded protein response in human adipose tissue. Diabetes 2014;63:912-922.Diabetes · 2014Article
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be a major contributor to many obesity-related pathologies. Little is known about what causes ER stress in obese people. Here, we show that insulin upregulated the unfolded protein response (UPR), an adaptive reaction to ER stress, in vitro in 3T3-L1 adipocytes and in vivo, in subcutaneous (sc) adipose tissue of nondiabetic subjects, where it increased the UPR dose dependently over the entire physiologic insulin range (from ∼ 35 to ∼ 1,450 pmol/L). The insulin-induced UPR was not due to increased glucose uptake/metabolism and oxidative stress. It was associated, however, with increased protein synthesis, with accumulation of ubiquitination associated proteins, and with multiple posttranslational protein modifications (acetylations, methylations, nitrosylations, succinylation, and ubiquitinations), some of which are potential causes for ER stress. These results reveal a new physiologic role of insulin and provide a putative mechanism for the development of ER stress in obesity. They may also have clinical and therapeutic implications, e.g., in diabetic patients treated with high doses of insulin.
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.