ArticleMolecular endocrinology (Baltimore, Md.)2012
PPAR-γ activation restores pancreatic islet SERCA2 levels and prevents β-cell dysfunction under conditions of hyperglycemic and cytokine stress.
Article in Molecular endocrinology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 117 citations in OpenAlex.
- Metabolic regulation of calcium homeostasis via SERCA succination.Science advances · 2026Article
- Organelle-specific crosstalk between calcium and redox signaling in pancreatic β-cells in physiology and type 2 diabetes.Frontiers in network physiology · 2026Review
- Molecular and Inflammatory Etiologies of β-Cell Dysfunction in Type 1 Diabetes.Physiology (Bethesda, Md.) · 2025Review
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Therapeutic Targeting of PPARγ in Nonalcoholic Fatty Liver Disease: Efficacy, Safety, and Drug Development.Drug design, development and therapy · 2025Review
- Article
- Sodium butyrate prevents cytokine-induced β-cell dysfunction through restoration of stromal interaction molecule 1 expression and activation of store-operated calcium entry.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- PDX1, a transcription factor essential for organ differentiation, regulates SERCA-dependent CaCell calcium · 2024Article
- Disrupted Endoplasmic Reticulum CaBiology · 2024Review
- The Ailing β-Cell in Diabetes: Insights From a Trip to the ER: The 2023 Outstanding Scientific Achievement Award Lecture.Diabetes · 2024Review
- Trimethylamine N-oxide impairs β-cell function and glucose tolerance.Nature communications · 2024Article
- Endoplasmic Reticulum Stress and Obesity.Advances in experimental medicine and biology · 2024Review
- SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells.Diabetologia · 2023Article
- Indirect comparison of efficacy and safety of chiglitazar and thiazolidinedione in patients with type 2 diabetes: A meta-analysis.World journal of diabetes · 2023Article
- Article
- CaBiomedicines · 2023Review
- THADA inhibition in mice protects against type 2 diabetes mellitus by improving pancreatic β-cell function and preserving β-cell mass.Nature communications · 2023Article
- Research progress on the mechanism of beta-cell apoptosis in type 2 diabetes mellitus.Frontiers in endocrinology · 2022Review
- Modulation of Gap Junction Coupling Within the Islet of Langerhans During the Development of Type 1 Diabetes.Frontiers in physiology · 2022Article
- SetD7 (Set7/9) is a novel target of PPARγ that promotes the adaptive pancreatic β-cell glycemic response.The Journal of biological chemistry · 2021Article
15 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The maintenance of intracellular Ca(2+) homeostasis in the pancreatic β-cell is closely regulated by activity of the sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA) pump. Our data demonstrate a loss of β-cell SERCA2b expression in several models of type 2 diabetes including islets from db/db mice and cadaveric diabetic human islets. Treatment of 832/13 rat INS-1-derived cells with 25 mm glucose and the proinflammatory cytokine IL-1β led to a similar loss of SERCA2b expression, which was prevented by treatment with the peroxisome proliferator-activated receptor (PPAR)-γ agonist, pioglitazone. Pioglitazone was able to also protect against hyperglycemia and cytokine-induced elevations in cytosolic Ca(2+) levels, insulin-secretory defects, and cell death. To determine whether PPAR-γ was a direct transcriptional regulator of the SERCA2 gene, luciferase assays were performed and showed that a -259 bp region is sufficient to confer PPAR-γ transactivation; EMSA and chromatin immunoprecipitation experiments confirmed that PPAR-γ directly binds a PPAR response element in this proximal region. We next sought to characterize the mechanisms by which SERCA2b was down-regulated. INS-1 cells were exposed to high glucose and IL-1β in time course experiments. Within 2 h of exposure, activation of cyclin-dependent kinase 5 (CDK5) was observed and correlated with increased serine-273 phosphorylation of PPAR-γ and loss of SERCA2 protein expression, findings that were prevented by pioglitazone and roscovitine, a pharmacological inhibitor of CDK5. We conclude that pioglitazone modulates SERCA2b expression through direct transcriptional regulation of the gene and indirectly through prevention of CDK5-induced phosphorylation of PPAR-γ.
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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.