Bis(maltolato)-oxovanadium (IV)-induced phosphorylation of PKB, GSK-3 and FOXO1 contributes to its glucoregulatory responses (review).
Over the last several decades, a large body of evidence has accumulated to suggest that organo-vanadium compounds (OVC) are more potent than inorganic vanadium salts in regulating hyperglycemia and insulin-resistance in rodent models of both type I and type II diabetes. Among these OVC, vanadium (IV) oxo bis(maltolato) (BMOV) was the first to be investigated for its higher potency over inorganic vanadium salts in eliciting insulin-like properties in both in vitro and in vivo systems. While the precise molecular mechanism by which BMOV exerts its insulin-mimetic effects remains poorly defined, studies have shown that BMOV is a potent activator of several key components of the insulin signaling pathways, such as phosphatidyl-inositol 3-kinase (PI3-K), and its downstream effector, protein kinase B (PKB). In addition, BMOV-induced phosphorylation of PKB has also been associated with the enhanced phosphorylation of glycogen synthase kinase-3 (GSK-3) and forkhead box protein 1 (FOXO1). Since PKB is instrumental in mediating the effects of insulin on glucose transport, glycogen synthesis and gluconeogenesis, it is reasonable to suggest that activation of this pathway by BMOV serves as a mechanism for its insulin-like effects.
Vardatsikos
George
G
Laboratory of Cell Signaling, Montreal Diabetes Research Center, Research Center-Centre Hospitalier de l'Université de Montréal and Department of Medicine, Université de Montréal, Montréal, Québec, H1W 4A4, Canada.
Mehdi
Mohamad Z
MZ
Srivastava
Ashok K
AK
D000818:Animals; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011753:Pyrones / Q000494:pharmacology*; D014638:Vanadates / Q000494:pharmacology*
D051858:Forkhead Transcription Factors; D011753:Pyrones; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005947:Glucose