Molecular mechanism of antidiabetic zinc-allixin complexes: regulations of glucose utilization and lipid metabolism.
J Biol Inorg Chem
; 13(5): 675-84, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18288506
ABSTRACT
We previously reported new zinc complexes of allixin [bis(allixinato)zinc] and its derivative bis(thioallixin-N-methyl)zinc that demonstrated excellent antidiabetic activity in type 2 diabetic mellitus KKA(y) mice. However, the molecular mechanism of these complexes is not fully understood. Thus, we attempted to reveal the intracellular mechanism of these complexes in 3T3-L1 adipocytes. Both zinc complexes induced Akt/protein kinase B (Akt/PKB) phosphorylation. The phosphorylation of Akt/PKB enhanced glucose transporter 4 translocation to the plasma membrane; this in turn enhanced the glucose utilization in a dose- and time-dependent manner. Glucose utilization by the complexes depended on the intracellular zinc concentration. Moreover, zinc complexes suppressed the cyclic AMP dependent protein kinase mediated phosphorylation of hormone-sensitive lipase (HSL), leading to the inhibition of free fatty acid release from the 3T3-L1 adipocytes. Such responses were inhibited by wortmannin, suggesting that the suppression of HSL by zinc complexes was dependent in the phosphoinositide 3-kinase-Akt/PKB signaling cascade. On the basis of these results, we proposed that both zinc complexes activated the Akt/PKB-mediated insulin-signaling pathway and improved both glucose utilization and lipid metabolism.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Fosfatidilinositol 3-Quinases
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Proteína Oncogênica v-akt
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Metabolismo dos Lipídeos
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Glucose
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Hipoglicemiantes
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article