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Cited by 497

The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

The Hyperglycemia-induced Inflammatory Response in Adipocytes

Open access
Lin, Ying, Berg, Anders H., Iyengar, Puneeth, Lam, Tony K.T., Giacca, Adria, Combs, Terry P., Rajala, Michael W., Du, Xueliang, Rollman, Brent, Li, Weijie, Hawkins, Meredith, Barzilai, Nir, Rhodes, Christopher J., Fantus, I. George, Brownlee, Michael, Scherer, Philipp E.·2005·Journal of Biological Chemistry

Abstract

Hyperglycemia is a major independent risk factor for diabetic macrovascular disease. The consequences of exposure of endothelial cells to hyperglycemia are well established. However, little is known about how adipocytes respond to both acute as well as chronic exposure to physiological levels of hyperglycemia. Here, we analyze adipocytes exposed to hyperglycemia both in vitro as well as in vivo. Comparing cells differentiated at 4 mm to cells differentiated at 25 mm glucose (the standard differentiation protocol) reveals severe insulin resistance in cells exposed to 25 mm glucose. A global assessment of transcriptional changes shows an up-regulation of a number of mitochondrial proteins. Exposure to hyperglycemia is associated with a significant induction of reactive oxygen species (ROS), both in vitro as well as in vivo in adipocytes isolated from streptozotocin-treated hyperglycemic mice. Furthermore, hyperglycemia for a few hours in a clamped setting will trigger the induction of a pro-inflammatory response in adipose tissue from rats that can effectively be reduced by co-infusion of N-acetylcysteine (NAC). ROS levels in 3T3-L1 adipocytes can be reduced significantly with pharmacological agents that lower the mitochondrial membrane potential, or by overexpression of uncoupling protein 1 or superoxide dismutase. In parallel with ROS, interleukin-6 secretion from adipocytes is significantly reduced. On the other hand, treatments that lead to a hyperpolarization of the mitochondrial membrane, such as overexpression of the mitochondrial dicarboxylate carrier result in increased ROS formation and decreased insulin sensitivity, even under normoglycemic conditions. Combined, these results highlight the importance ROS production in adipocytes and the associated insulin resistance and inflammatory response.

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Metadata

Authors
Lin, Y., Berg, A. H., Iyengar, P., Lam, T. K. T., Giacca, A., Combs, T. P., Rajala, M. W., Du, X., Rollman, B., Li, W., Hawkins, M., Barzilai, N., Rhodes, C. J., Fantus, I. G., Brownlee, M., & Scherer, P. E.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2005-02
Volume
280
Issue
6
Pages
4617-4626
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2159229970
Cited by
497
References
10
FWCI
16.21
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: The Hyperglycemia-induced Inflammatory Response in Adipocytes. https://app.cochat.ai/papers/10.1074/jbc.m411863200
The paper
Lin, Y., Berg, A. H., Iyengar, P., Lam, T. K. T., Giacca, A., Combs, T. P., Rajala, M. W., Du, X., Rollman, B., Li, W., Hawkins, M., Barzilai, N., Rhodes, C. J., Fantus, I. G., Brownlee, M., & Scherer, P. E. (2005). The Hyperglycemia-induced Inflammatory Response in Adipocytes. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m411863200

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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