Journal
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
Volume 10, Issue 8, Pages 874-886Publisher
SPRINGER
DOI: 10.1007/s00775-005-0037-x
Keywords
adipocyte; diabetes; insulin receptor and insulin receptor substrate; insulin signaling; tyrosine phosphorylation; vanadyl
Funding
- NIDDK NIH HHS [DK20959, DK57599] Funding Source: Medline
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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 beta-subunit of the insulin receptor (IR beta) 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 beta, IRS1, protein kinase B, and glycogen synthase kinase-3 beta. Wortmannin suppressed all of these classical insulin-signaling activities exerted by VO(acac)(2) or insulin, except for tyrosine phosphorylation of IR beta 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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