The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Polyphenols Stimulate AMP-Activated Protein Kinase, Lower Lipids, and Inhibit Accelerated Atherosclerosis in Diabetic LDL Receptor–Deficient Mice
Open accessAbstract
Because polyphenols may have beneficial effects on dyslipidemia, which accelerates atherosclerosis in diabetes, we examined the effect of polyphenols on hepatocellular AMP-activated protein kinase (AMPK) activity and lipid levels, as well as hyperlipidemia and atherogenesis in type 1 diabetic LDL receptor–deficient mice (DMLDLR−/−). In HepG2 hepatocytes, polyphenols, including resveratrol (a major polyphenol in red wine), apigenin, and S17834 (a synthetic polyphenol), increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC), and they increased activity of AMPK with 200 times the potency of metformin. The polyphenols also prevented the lipid accumulation that occurred in HepG2 cells exposed to high glucose, and their ability to do so was mimicked and abrogated, respectively, by overexpression of constitutively active and dominant-negative AMPK mutants. Furthermore, treatment of DMLDLR−/− mice with S17834 prevented the decrease in AMPK and ACC phosphorylation and the lipid accumulation in the liver, and it also inhibited hyperlipidemia and the acceleration of aortic lesion development. These studies 1) reveal that inactivation of hepatic AMPK is a key event in the pathogenesis of hyperlipidemia in diabetes, 2) point to a novel mechanism of action of polyphenols to lower lipids by activating AMPK, and 3) emphasize a new therapeutic avenue to benefit hyperlipidemia and atherosclerosis specifically in diabetes via activating AMPK.
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Cites
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
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Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
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Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
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The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
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LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
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Peroxisome-Proliferator-Activated Receptor δ Activates Fat Metabolism to Prevent Obesity
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Adiponectin-mediated modulation of hypertrophic signals in the heart
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Cited by
Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290
The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923
AMPK and SIRT1: a long-standing partnership?
Ruderman, N. B., Julia Xu, X., Nelson, L., Cacicedo, J. M., Saha, A. K., Lan, F., & Ido, Y. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00745.2009 · Cited by 903
Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets
Drummond, G. R., Selemidis, S., Griendling, K. K., & Sobey, C. G. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3403 · Cited by 899
SIRT1 Regulates Hepatocyte Lipid Metabolism through Activating AMP-activated Protein Kinase
Hou, X., Xu, S., Maitland-Toolan, K. A., Sato, K., Jiang, B., Ido, Y., Lan, F., Walsh, K., Wierzbicki, M., Verbeuren, T. J., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802187200 · Cited by 778
Self-citation
Metadata
- Authors
- Zang, M., Xu, S., Maitland-Toolan, K. A., Zuccollo, A., Hou, X., Jiang, B., Wierzbicki, M., Verbeuren, T. J., & Cohen, R. A.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2006-08-01
- Volume
- 55
- Issue
- 8
- Pages
- 2180-2191
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2103450921
- Cited by
- 664
- References
- 11
- FWCI
- 15.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Zang, M., Xu, S., Maitland-Toolan, K. A., Zuccollo, A., Hou, X., Jiang, B., Wierzbicki, M., Verbeuren, T. J., & Cohen, R. A. (2006). Polyphenols Stimulate AMP-Activated Protein Kinase, Lower Lipids, and Inhibit Accelerated Atherosclerosis in Diabetic LDL Receptor–Deficient Mice. Diabetes. https://doi.org/10.2337/db05-1188
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