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Cited by 456

The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.

AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function

Open access
Dugan, Laura L., You, Young-Hyun, Ali, Sameh S., Diamond-Stanic, Maggie, Miyamoto, Satoshi, DeCleves, Anne-Emilie, Andreyev, Aleksander, Quach, Tammy, Ly, San, Shekhtman, Grigory, Nguyen, William, Chepetan, Andre, Le, Thuy P., Wang, Lin, Xu, Ming, Paik, Kacie P., Fogo, Agnes, Viollet, Benoit, Murphy, Anne, Brosius, Frank, Naviaux, Robert K., Sharma, Kumar·2013·Journal of Clinical Investigation

Abstract

Diabetic microvascular complications have been considered to be mediated by a glucose-driven increase in mitochondrial superoxide anion production. Here, we report that superoxide production was reduced in the kidneys of a steptozotocin-induced mouse model of type 1 diabetes, as assessed by in vivo real-time transcutaneous fluorescence, confocal microscopy, and electron paramagnetic resonance analysis. Reduction of mitochondrial biogenesis and phosphorylation of pyruvate dehydrogenase (PDH) were observed in kidneys from diabetic mice. These observations were consistent with an overall reduction of mitochondrial glucose oxidation. Activity of AMPK, the major energy-sensing enzyme, was reduced in kidneys from both diabetic mice and humans. Mitochondrial biogenesis, PDH activity, and mitochondrial complex activity were rescued by treatment with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). AICAR treatment induced superoxide production and was linked with glomerular matrix and albuminuria reduction in the diabetic kidney. Furthermore, diabetic heterozygous superoxide dismutase 2 (Sod2(+/-)) mice had no evidence of increased renal disease, and Ampka2(-/-) mice had increased albuminuria that was not reduced with AICAR treatment. Reduction of mitochondrial superoxide production with rotenone was sufficient to reduce AMPK phosphorylation in mouse kidneys. Taken together, these results demonstrate that diabetic kidneys have reduced superoxide and mitochondrial biogenesis and activation of AMPK enhances superoxide production and mitochondrial function while reducing disease activity.

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Metadata

Authors
Dugan, L. L., You, Y.-H., Ali, S. S., Diamond-Stanic, M., Miyamoto, S., DeCleves, A.-E., Andreyev, A., Quach, T., Ly, S., Shekhtman, G., Nguyen, W., Chepetan, A., Le, T. P., Wang, L., Xu, M., Paik, K. P., Fogo, A., Viollet, B., Murphy, A., Brosius, F., Naviaux, R. K., & Sharma, K.
Venue
Journal of Clinical Investigation
Published
2013-10-25
Volume
123
Issue
11
Pages
4888-4899
ISSN
0021-9738 (ISSN-L)
OpenAlex
W2110174113
Cited by
456
References
9
FWCI
15.06
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. https://app.cochat.ai/papers/10.1172/jci66218
The paper
Dugan, L. L., You, Y.-H., Ali, S. S., Diamond-Stanic, M., Miyamoto, S., DeCleves, A.-E., Andreyev, A., Quach, T., Ly, S., Shekhtman, G., Nguyen, W., Chepetan, A., Le, T. P., Wang, L., Xu, M., Paik, K. P., Fogo, A., Viollet, B., Murphy, A., . . . Sharma, K. (2013). AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. Journal of Clinical Investigation. https://doi.org/10.1172/jci66218

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

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.