The vanadyl (VO2+) chelate bis(acetylacetonato)oxovanadium(IV) potentiates tyrosine phosphorylation of the insulin receptor |
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| Authors: | Hesheng Ou Limei Yan Devkumar Mustafi Marvin W. Makinen Matthew J. Brady |
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| Affiliation: | (1) Department of Medicine and Committee on Molecular Metabolism and Nutrition, The University of Chicago, MC1027, 5841 S. Maryland Ave, Chicago, IL 60637, USA;(2) Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA |
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| Abstract: | We have compared the insulin-like activity of bis(acetylacetonato)oxovanadium(IV) [VO(acac)2], bis(maltolato)oxovanadium(IV) [VO(malto)2], and bis(1-N-oxide-pyridine-2-thiolato)oxovanadium(IV) [VO(OPT)2] in differentiated 3T3-L1 adipocytes. The insulin-like influence of VO(malto)2 and VO(OPT)2 was decreased compared with that of VO(acac)2. Also, serum albumin enhanced the insulin-like activity of all three chelates more than serum transferrin. Each of the three VO2+ chelates increased the tyrosine phosphorylation of proteins in response to insulin, including the β-subunit of the insulin receptor (IRβ) and the insulin receptor substrate-1 (IRS1). However, VO(acac)2 exhibited the greatest synergism with insulin and was therefore further investigated. Treatment of 3T3-L1 adipocytes with 0.25 mM VO(acac)2 in the presence of 0.25 mM serum albumin synergistically increased glycogen accumulation stimulated by 0.1 and 1 nM insulin, and increased the phosphorylation of IRβ, IRS1, protein kinase B, and glycogen synthase kinase-3β. Wortmannin suppressed all of these classical insulin-signaling activities exerted by VO(acac)2 or insulin, except for tyrosine phosphorylation of IRβ and IRS1. Additionally, VO(acac)2 enhanced insulin signaling and metabolic action in insulin-resistant 3T3-L1 adipocytes. Cumulatively, these results provide evidence that VO(acac)2 exerts its insulin-enhancing properties by directly potentiating the tyrosine phosphorylation of the insulin receptor, resulting in the initiation of insulin metabolic signaling cascades in 3T3-L1 adipocytes. |
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| Keywords: | Adipocyte Diabetes Insulin receptor and insulin receptor substrate Insulin signaling Tyrosine phosphorylation Vanadyl |
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