The vanadyl (VO2+) chelate bis(acetylacetonato)oxovanadium(IV) potentiates tyrosine phosphorylation of the insulin receptor.
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 (IRbeta) 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 IRbeta, IRS1, protein kinase B, and glycogen synthase kinase-3beta. Wortmannin suppressed all of these classical insulin-signaling activities exerted by VO(acac)2 or insulin, except for tyrosine phosphorylation of IRbeta 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.
Ou
Hesheng
H
Department of Medicine and Committee on Molecular Metabolism and Nutrition, The University of Chicago, MC1027, 5841 S. Maryland Ave, Chicago, IL 60637, USA.
Yan
Limei
L
Mustafi
Devkumar
D
Makinen
Marvin W
MW
Brady
Matthew J
MJ
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D004789:Enzyme Activation; D006003:Glycogen / Q000096:biosynthesis; D006006:Glycogen Synthase / Q000187:drug effects / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000494:pharmacology; D010766:Phosphorylation; D011753:Pyrones / Q000494:pharmacology; D011972:Receptor, Insulin / Q000187:drug effects* / Q000378:metabolism; D012996:Solutions / Q000737:chemistry; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
D002614:Chelating Agents; D007004:Hypoglycemic Agents; D009942:Organometallic Compounds; D011753:Pyrones; D012996:Solutions; C507910:bis(1-N-oxide-pyridine-2-thiolato)oxovanadium(IV); C507909:bis(acetylacetonato)oxovanadium(IV); C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates; D014443:Tyrosine; D006003:Glycogen; D006006:Glycogen Synthase; D011972:Receptor, Insulin