ArticleThe Journal of biological chemistry2016
Peroxisome Proliferator-activated Receptor-γ Activation Augments the β-Cell Unfolded Protein Response and Rescues Early Glycemic Deterioration and β Cell Death in Non-obese Diabetic Mice.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Practice guideline: Statement regarding treatment for suspected slowly progressive type 1 diabetes (SPIDDM; probable) cases (English version).Journal of diabetes investigation · 2025Guideline
- Synthetic Immunological Niche Reveals Early Immune Dysregulation and Stratifies Therapeutic Response in Type 1 Diabetes.bioRxiv : the preprint server for biology · 2026Article
- Effect of Pioglitazone on Endoplasmic Reticulum Stress and Autophagy Response in the Perivascular Adipose Tissue of Type 2 Diabetic Rats.PPAR research · 2025Article
- Practice guideline: Statement regarding treatment for suspected slowly progressive type 1 diabetes (SPIDDM; probable) cases (English Version).Diabetology international · 2025Article
- Relevant Serum Endoplasmic Reticulum Stress Biomarkers in Type 2 Diabetes and Its Complications: A Systematic Review and Meta-Analysis.Antioxidants (Basel, Switzerland) · 2024Review
- GDF15: a potential therapeutic target for type 1 diabetes.Expert opinion on therapeutic targets · 2022Review
- Immunological balance between Treg and Th17 lymphocytes as a key element of type 1 diabetes progression in children.Frontiers in immunology · 2022Article
- New Aspects of Diabetes Research and Therapeutic Development.Pharmacological reviews · 2021Review
- The role of beta-cell dysfunction in early type 1 diabetes.Current opinion in endocrinology, diabetes, and obesity · 2020Review
- Comprehensive Proteomics Analysis of Stressed Human Islets Identifies GDF15 as a Target for Type 1 Diabetes Intervention.Cell metabolism · 2020Article
- Targeting dysfunctional beta-cell signaling for the potential treatment of type 1 diabetes mellitus.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- Inhibition of hepatocyte nuclear factor 1b induces hepatic steatosis through DPP4/NOX1-mediated regulation of superoxide.Free radical biology & medicine · 2017Article
- Article
- Pancreatic β-cell protection from inflammatory stress by the endoplasmic reticulum proteins thrombospondin 1 and mesencephalic astrocyte-derived neutrotrophic factor (MANF).The Journal of biological chemistry · 2017Article
- Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.Molecular metabolism · 2017Review
- Distinct but complementary contributions of PPAR isotypes to energy homeostasis.The Journal of clinical investigation · 2017Review
- Fatty acid-mediated signaling as a target for developing type 1 diabetes therapies.Expert opinion on therapeutic targetsReview
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 2 institutions in 2 countries.
Funding
Abstract
Type 1 diabetes is an autoimmune disorder that is characterized by a failure of the unfolded protein response in islet β cells with subsequent endoplasmic reticulum stress and cellular death. Thiazolidinediones are insulin sensitizers that activate the nuclear receptor PPAR-γ and have been shown to partially ameliorate autoimmune type 1 diabetes in humans and non-obese diabetic (NOD) mice. We hypothesized that thiazolidinediones reduce β cell stress and death independently of insulin sensitivity. To test this hypothesis, female NOD mice were administered pioglitazone during the pre-diabetic phase and assessed for insulin sensitivity and β cell function relative to controls. Pioglitazone-treated mice showed identical weight gain, body fat distribution, and insulin sensitivity compared with controls. However, treated mice showed significantly improved glucose tolerance with enhanced serum insulin levels, reduced β cell death, and increased β cell mass. The effect of pioglitazone was independent of actions on T cells, as pancreatic lymph node T cell populations were unaltered and T cell proliferation was unaffected by pioglitazone. Isolated islets of treated mice showed a more robust unfolded protein response, with increases in Bip and ATF4 and reductions in spliced Xbp1 mRNA. The effect of pioglitazone appears to be a direct action on β cells, as islets from mice treated with pioglitazone showed reductions in PPAR-γ (Ser-273) phosphorylation. Our results demonstrate that PPAR-γ activation directly improves β cell function and survival in NOD mice by enhancing the unfolded protein response and suggest that blockade of PPAR-γ (Ser-273) phosphorylation may prevent type 1 diabetes.
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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 Socratic graph.