ArticleBiochemical pharmacology2010
Tiam1/Rac1 signaling pathway mediates palmitate-induced, ceramide-sensitive generation of superoxides and lipid peroxides and the loss of mitochondrial membrane potential in pancreatic beta-cells.
Article in Biochemical pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
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- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.bioRxiv : the preprint server for biology · 2026Article
- Feeding the invaders: how metabolic imbalance shapes infection and biofilm development.FEMS microbiology reviews · 2026Review
- Organelle-specific crosstalk between calcium and redox signaling in pancreatic β-cells in physiology and type 2 diabetes.Frontiers in network physiology · 2026Review
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- Alpha4 contributes to the dysfunction of the pancreatic beta cell under metabolic stress.Molecular and cellular endocrinology · 2022Article
- Regulation of serine palmitoyl-transferase and Rac1-Nox2 signaling in diabetic retinopathy.Scientific reports · 2022Article
- Autotaxin signaling facilitates β cell dedifferentiation and dysfunction induced by Sirtuin 3 deficiency.Molecular metabolism · 2022Article
- CARD9 Mediates Pancreatic Islet Beta-Cell Dysfunction Under the Duress of Hyperglycemic Stress.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2022Article
- PRDX6: A protein bridging S-palmitoylation and diabetic neuropathy.Frontiers in endocrinology · 2022Article
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Review
- Paradoxical regulation of glucose-induced Rac1 activation and insulin secretion by RhoGDIβ in pancreatic β-cells.Small GTPases · 2021Article
- P-Rex1 Mediates Glucose-Stimulated Rac1 Activation and Insulin Secretion in Pancreatic β-Cells.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2020Article
- Association between ceramides and coronary artery stenosis in patients with coronary artery disease.Lipids in health and disease · 2020Article
- GPCRs, G Proteins, and Their Impact on β-cell Function.Comprehensive Physiology · 2020Review
- Lipid oversupply induces CD36 sarcolemmal translocation via dual modulation of PKCζ and TBC1D1: an early event prior to insulin resistance.Theranostics · 2020Article
- Quantitative proteomics reveals novel interaction partners of Rac1 in pancreatic β-cells: Evidence for increased interaction with Rac1 under hyperglycemic conditions.Molecular and cellular endocrinology · 2019Article
- RACking up ceramide-induced islet β-cell dysfunction.Biochemical pharmacology · 2018Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The phagocytic NADPH oxidase [NOX] has been implicated in the generation of superoxides in the pancreatic beta-cell. Herein, using normal rat islets and clonal INS 832/13 cells, we tested the hypothesis that activation of the small G-protein Rac1, which is a member of the NOX holoenzyme, is necessary for palmitate [PA]-induced generation of superoxides in pancreatic beta-cells. Incubation of isolated beta-cells with PA potently increased the NOX activity culminating in a significant increase in the generation of superoxides and lipid peroxides in these cells; such effects of PA were attenuated by diphenyleneiodonium [DPI], a known inhibitor of NOX. In addition, PA caused a transient, but significant activation [i.e., GTP-bound form] of Rac1 in these cells. NSC23766, a selective inhibitor of Rac1, but not Cdc42 or Rho activation, inhibited Rac1 activation and the generation of superoxides and lipid peroxides induced by PA. Fumonisin B-1 [FB-1], which inhibits de novo synthesis of ceramide [CER] from PA, also attenuated PA-induced superoxide and lipid peroxide generation and NOX activity implicating intracellularly generated CER in the metabolic effects of PA; such effects were also demonstrable in the presence of the cell-permeable C2-CER. Further, NSC23766 prevented C2-CER-induced Rac1 activation and production of superoxides and lipid peroxides. Lastly, C2-CER, but not its inactive analogue, significantly reduced the mitochondrial membrane potential, which was prevented to a large degree by NSC23766. Together, our findings suggest that Tiam1/Rac1 signaling pathway regulates PA-induced, CER-dependent superoxide generation and mitochondrial dysfunction in pancreatic beta-cells.
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