| Akt inhibitors reduce glucose uptake independently of their effects on Akt. | |
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MedLine Citation:
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PMID: 20819080 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The protein kinase Akt is involved in various cellular processes, including cell proliferation, growth and metabolism. Hyperactivation of Akt is commonly observed in human tumours and so this pathway has been the focus of targeted drug discovery. However, Akt also plays an essential role in other physiological processes, such as the insulin-regulated transport of glucose into muscle and fat cells. This process, which is essential for whole-body glucose homoeostasis in mammals, is thought to be mediated via Akt-dependent movement of GLUT4 glucose transporters to the plasma membrane. In the present study, we have investigated the metabolic side effects of non-ATP-competitive allosteric Akt inhibitors. In 3T3-L1 adipocytes, these inhibitors caused a decrease in the Akt signalling pathway concomitant with reduced glucose uptake. Surprisingly, a similar reduction in GLUT4 translocation to the plasma membrane was not observed. Further investigation revealed that the inhibitory effects of these compounds on glucose uptake in 3T3-L1 adipocytes were independent of the Akt signalling pathway. The inhibitors also inhibited glucose transport into other cell types, including human erythrocytes and T-47D breast cancer cells, suggesting that these effects are not specific to GLUT4. We conclude that these drugs may, at least in part, inhibit tumorigenesis through inhibition of tumour cell glucose transport. |
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Authors:
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Shi-Xiong Tan; Yvonne Ng; David E James |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 432 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-25 Completed Date: 2010-12-06 Revised Date: 2011-09-06 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 191-7 Citation Subset: IM |
Affiliation:
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The Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3-L1 Cells Adipocytes / cytology, drug effects, metabolism Animals Biological Transport / drug effects Blotting, Western Breast Neoplasms / metabolism, pathology Cell Line, Tumor Cell Membrane / metabolism Erythrocytes / drug effects, metabolism Female Glucose / pharmacokinetics* Glucose Transporter Type 4 / metabolism Humans Mice Phosphorylation / drug effects Protein Kinase Inhibitors / pharmacology* Protein Transport / drug effects Proto-Oncogene Proteins c-akt / antagonists & inhibitors*, metabolism Signal Transduction / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Glucose Transporter Type 4; 0/Protein Kinase Inhibitors; 0/SLC2A4 protein, human; 50-99-7/Glucose; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
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