Phenylarsine oxide and the mechanism of insulin-stimulated sugar transport.
The actions of phenylarsine oxide (PAO) on hormone receptors and transport processes are reviewed with particular reference to the mechanism of insulin-stimulated sugar transport. It is suggested that as well as reaction with vicinal -SH groups, vicinal -SH/-OH and -SH/-CO2H groups should also be considered as potential reaction sites for PAO. The relatively high levels of these vicinal combinations of groups in many hormone receptors makes them particularly susceptible to reaction with PAO. In the case of insulin-stimulated sugar transport PAO does not inhibit insulin binding to its receptor at low concentrations but may react directly with the glucose transporters in some cells. A hypothesis is proposed suggesting that PAO may react specifically with one transporter isoform (GLUT-4) which is found almost exclusively in rat adipocytes, skeletal muscle and heart tissue (i.e. insulin responsive tissue) whereas in insulin unresponsive cells such as erythrocytes the GLUT-1 isoform is the predominant transporter which is not inhibited by PAO.
Douen
A G
AG
Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Jones
M N
MN
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D050260:Carbohydrate Metabolism; D003864:Depression, Chemical; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007329:Insulin Antagonists / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism
D001152:Arsenicals; D007328:Insulin; D007329:Insulin Antagonists; D009004:Monosaccharide Transport Proteins; D011956:Receptors, Cell Surface; C029341:oxophenylarsine; D011972:Receptor, Insulin