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 accessAbstract
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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Citations
Cites
Biochemistry and molecular cell biology of diabetic complications
Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
Nishikawa, T., Edelstein, D., Du, X. L., Yamagishi, S.-I., Matsumura, T., Kaneda, Y., Yorek, M. A., Beebe, D., Oates, P. J., Hammes, H.-P., et al. (2000) · Nature · doi:10.1038/35008121 · Cited by 4,277
Circulating mitochondrial DAMPs cause inflammatory responses to injury
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Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., et al. (2005) · Science · doi:10.1126/science.1112125 · Cited by 2,165
The key role of anaplerosis and cataplerosis for citric acid cycle function
Owen, O. E., Kalhan, S. C., & Hanson, R. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.r200006200 · Cited by 1,172 · cited 2×
“Mitochondria respond to the caloric availability of the cell by following 2 major pathways: anaplerosis or cataplerosis (30).”
Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase
Behrens, M. M., Ali, S. S., Dao, D. N., Lucero, J., Shekhtman, G., Quick, K. L., & Dugan, L. L. (2007) · Science · doi:10.1126/science.1148045 · Cited by 585
Self-citationMetabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease
Sharma, K., Karl, B., Mathew, A. V., Gangoiti, J. A., Wassel, C. L., Saito, R., Pu, M., Sharma, S., You, Y.-H., Wang, L., et al. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013020126 · Cited by 571
Self-citationPhysiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models
Viollet, B., Andreelli, F., Jørgensen, S. B., Perrin, C., Flamez, D., Mu, J., Wojtaszewski, J. F. P., Schuit, F. C., Birnbaum, M., Richter, E., et al. (2003) · Biochemical Society Transactions · doi:10.1042/bst0310216 · Cited by 241 · cited 1×
“…validate that AMPK is the critical enzyme responsible for regulating mitochondrial function in diabetic kidney disease, additional studies were performed with a model of progressive diabetic kidney disease (the F1 cross of DBA2J and C57BL/6J with Akita) (27, 28) and with the Ampka2 –/– mice (29).”
Self-citationDugan, L. L., Ali, S. S., Shekhtman, G., Roberts, A. J., Lucero, J., Quick, K. L., & Behrens, M. M. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005518 · Cited by 165 · cited 4×
“To demonstrate that DHE was not handled differently in the diabetic kidney, [ 14 C]-labeled DHE was synthesized using 1 mCi [ 14 C]-ring benzoic acid, [ring-u-14C] (Chemdepo Inc.) to produce [ 14 C]-labeled ethidium as described (46).”
InfluentialSelf-citation
Cited by
Kang, H. M., Ahn, S. H., Choi, P., Ko, Y.-A., Han, S. H., Chinga, F., Park, A. S. D., Tao, J., Sharma, K., Pullman, J., et al. (2015) · Nature Medicine · doi:10.1038/nm.3762 · Cited by 1,555
Self-citationDiabetes and Kidney Disease: Role of Oxidative Stress
Jha, J. C., Banal, C., Chow, B. S. M., Cooper, M. E., & Jandeleit-Dahm, K. (2016) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6664 · Cited by 660
Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease
Sharma, K., Karl, B., Mathew, A. V., Gangoiti, J. A., Wassel, C. L., Saito, R., Pu, M., Sharma, S., You, Y.-H., Wang, L., et al. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013020126 · Cited by 571
Self-citationMitochondrial quality control in kidney injury and repair
Tang, C., Cai, J., Yin, X.-M., Weinberg, J. M., Venkatachalam, M. A., & Dong, Z. (2021) · Nature Reviews Nephrology · doi:10.1038/s41581-020-00369-0 · Cited by 513
The hallmarks of mitochondrial dysfunction in chronic kidney disease
Galvan, D. L., Green, N. H., & Danesh, F. R. (2017) · Kidney International · doi:10.1016/j.kint.2017.05.034 · Cited by 447
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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- 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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