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- Title
The vanadyl (VO<sup>2+</sup>) chelate bis(acetylacetonato)oxovanadium(IV) potentiates tyrosine phosphorylation of the insulin receptor.
- Authors
Ou, Hesheng; Yan, Limei; Mustafi, Devkumar; Makinen, Marvin; Brady, Matthew
- 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 (IR β) 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 IR β, IRS1, protein kinase B, and glycogen synthase kinase-3 β. Wortmannin suppressed all of these classical insulin-signaling activities exerted by VO(acac)2 or insulin, except for tyrosine phosphorylation of IR β 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.
- Subjects
INSULIN; FAT cells; DIABETES; TYROSINE; DIMETHYL sulfoxide; ELECTRON paramagnetic resonance; SALINE solutions; PHOSPHORYLATION; CHEMICAL reactions
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2005, Vol 10, Issue 8, p874
- ISSN
0949-8257
- Publication type
Article
- DOI
10.1007/s00775-005-0037-x