ArticleDiabetologia2011
Deletion of protein kinase Cδ in mice modulates stability of inflammatory genes and protects against cytokine-stimulated beta cell death in vitro and in vivo.
Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Mechanistic insights into the anti-inflammatory effects of isocoronarin D associated with reduced PKCδ and PI3K/Akt signalling in LPS-activated macrophages.Inflammopharmacology · 2026Article
- Cell Therapy for T1D Beyond BLA: Gearing Up Toward Clinical Practice.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2025Review
- The future of islet transplantation beyond the BLA approval: challenges and opportunities.Frontiers in transplantation · 2025Review
- Regulatory roles of CARD9-BCL10-Rac1 (CBR) signalome in islet β-cell function in health and metabolic stress: Is there room for MALT1?Biochemical pharmacology · 2023Review
- Regulatory Roles of Histone Deacetylation in Metabolic Stress-Induced Expression of Caspase Recruitment Domain-Containing Protein 9 (CARD9) in Pancreatic β-Cells.International journal of molecular sciences · 2023Article
- Islet cells in human type 1 diabetes: from recent advances to novel therapies - a symposium-based roadmap for future research.The Journal of endocrinology · 2023Review
- Bioactive lipids and metabolic syndrome-a symposium report.Annals of the New York Academy of Sciences · 2022Article
- Functional proteomic analysis reveals roles for PKCδ in regulation of cell survival and cell death: Implications for cancer pathogenesis and therapy.Advances in biological regulation · 2020Article
- Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review.Lipids in health and disease · 2020Review
- Phenotype of a transient neonatal diabetes point mutation (SUR1-R1183W) in mice.Wellcome open research · 2020Article
- Tip60- and sirtuin 2-regulated MARCKS acetylation and phosphorylation are required for diabetic embryopathy.Nature communications · 2019Article
- Disruption of beta cell acetyl-CoA carboxylase-1 in mice impairs insulin secretion and beta cell mass.Diabetologia · 2019Article
- Protein kinase C isoforms in the normal pancreas and in pancreatic disease.Cellular signalling · 2017Review
- Inhibition of Y1 receptor signaling improves islet transplant outcome.Nature communications · 2017Article
- Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance.Molecular and cellular biochemistry · 2017Review
- Multifunctional roles of PKCδ: Opportunities for targeted therapy in human disease.Pharmacology & therapeutics · 2016Review
- Low Level Pro-inflammatory Cytokines Decrease Connexin36 Gap Junction Coupling in Mouse and Human Islets through Nitric Oxide-mediated Protein Kinase Cδ.The Journal of biological chemistry · 2016Article
- Protein kinase Cδ regulates nuclear export of FOXO1 through phosphorylation of the chaperone 14-3-3ζ.Diabetologia · 2015Article
- DOC2 isoforms play dual roles in insulin secretion and insulin-stimulated glucose uptake.Diabetologia · 2014Article
- Identification of fatty acid binding protein 4 as an adipokine that regulates insulin secretion during obesity.Molecular metabolism · 2014Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisProinflammatory cytokines contribute to beta cell destruction in type 1 diabetes, but the mechanisms are incompletely understood. The aim of the current study was to address the role of the protein kinase C (PKC) isoform PKCδ, a diverse regulator of cell death, in cytokine-stimulated apoptosis in primary beta cells.
methodsIslets isolated from wild-type or Prkcd(-/-) mice were treated with IL-1β, TNF-α and IFNγ and assayed for apoptosis, nitric oxide (NO) generation and insulin secretion. Activation of signalling pathways, apoptosis and endoplasmic reticulum (ER) stress were determined by immunoblotting. Stabilisation of mRNA transcripts was measured by RT-PCR following transcriptional arrest. Mice were injected with multiple low doses of streptozotocin (MLD-STZ) and fasting blood glucose monitored.
resultsDeletion of Prkcd inhibited apoptosis and NO generation in islets stimulated ex vivo with cytokines. It also delayed the onset of hyperglycaemia in MLD-STZ-treated mice. Activation of ERK, p38, JNK, AKT1, the ER stress markers DDIT3 and phospho-EIF2α and the intrinsic apoptotic markers BCL2 and MCL1 was not different between genotypes. However, deletion of Prkcd destabilised mRNA transcripts for Nos2, and for multiple components of the toll-like receptor 2 (TLR2) signalling complex, which resulted in disrupted TLR2 signalling. CONCLUSIONS/
interpretationLoss of PKCδ partially protects against hyperglycaemia in the MLD-STZ model in vivo, and against cytokine-mediated apoptosis in vitro. This is accompanied by reduced NO generation and destabilisation of Nos2 and components of the TLR2 signalling pathway. The results highlight a mechanism for regulating proinflammatory gene expression in beta cells independently of transcription.
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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.