Cited by 120Redox biology and oxidative stressAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

PKC-δ-dependent activation of oxidative stress in adipocytes of obese and insulin-resistant mice: role for NADPH oxidase

Talior, Ilana, Tennenbaum, Tamar, Kuroki, Toshio, Eldar-Finkelman, Hagit·2005·American Journal of Physiology-Endocrinology and Metabolism

Abstract

Oxidative stress is thought to be one of the causative factors contributing to insulin resistance and type 2 diabetes. Previously, we showed that reactive oxygen species (ROS) production is significantly increased in adipocytes from high-fat diet-induced obese and insulin-resistant mice (HF). ROS production was also associated with the increased activity of PKC-δ. In the present studies, we hypothesized that PKC-δ contributes to ROS generation and determined their intracellular source. NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) reduced ROS levels by 50% in HF adipocytes, and inhibitors of NO synthase (l-NAME, 1 mM), xanthine oxidase (allopurinol, 100 μM), AGE formation (aminoguanidine, 10 μM), or the mitochondrial uncoupler (FCCP, 10 μM) had no effect. Rottlerin, a selective PKC-δ inhibitor, suppressed ROS levels by ∼50%. However, neither GÖ-6976 nor LY-333531, effective inhibitors toward conventional PKC or PKC-β, respectively, significantly altered ROS levels in HF adipocytes. Subsequently, adenoviral-mediated expression of wild-type PKC-δ or its dominant negative mutant (DN-PKC-δ) in HF adipocytes resulted in either a twofold increase in ROS levels or their suppression by 20%, respectively. In addition, both ROS levels and PKC-δ activity were sharply reduced by glucose depletion. Taken together, these results suggest that PKC-δ is responsible for elevated intracellular ROS production in HF adipocytes, and this is mediated by high glucose and NADPH oxidase.

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Crossref · 10.1152/ajpendo.00378.2004

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  • By suppressing adipocyte oxidative stress, spirulina may lead to systemic anti-inflammatory and insulin-sensitising effects.

    “Thus, by suppressing adipocyte oxidative stress, spirulina may lead to systemic anti-inflammatory and insulin-sensitising effects.12–20”

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Authors
Talior, I., Tennenbaum, T., Kuroki, T., & Eldar-Finkelman, H.
Venue
American Journal of Physiology-Endocrinology and Metabolism
Published
2005-02
Volume
288
Issue
2
Pages
E405-E411
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
OpenAlex
W1913740938
Cited by
120
References
51
Citations by year
2025: 3 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 9 · 2013: 4 · 2012: 5
FWCI
3.19
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
PKCδ, oxidative stress, adipocytes, insulin resistance, obesity, NADPH oxidase, reactive oxygen species, high-fat diet, diphenyleneiodonium, glucose depletion, type 2 diabetes, adipose tissue
MeSH terms
Animals, Cells, Cultured, Dietary Fats, Dose-Response Relationship, Drug, Enzyme Activation, Insulin Resistance, Mice, Inbred C57BL, Obesity, Onium Compounds, Protein Kinase C, Reactive Oxygen Species, Adipocytes, Oxidative Stress, NADPH Oxidases, Mice, Protein Kinase C-delta

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