Effect of vanadate on glycogen synthesis in dexamethasone-treated 3T3 adipocytes: evidence for a novel insulin sensitizing action.
OBJECTIVE
Type 2 diabetes is characterized by peripheral tissue insulin resistance. The present study was carried out to determine the insulin sensitizing action of vanadium using dexamethasone-treated 3T3 adipocytes as an in-vitro model of insulin resistance.


METHODS
Fully differentiated 3T3 adipocytes were incubated with or without 100 nM dexamethasone in the presence or absence of 200 nM insulin for 6 days. Sodium orthovanadate (0-1000 microM) was added on day 2 and was present during the last 4 days. At the end, insulin (100 nM) stimulated glycogen synthesis was determined.


RESULTS
Vanadate treatment for 4 days, caused 2-3-fold increase in glycogen synthesis in dexamethasone treated adipocytes. At 100 microM, vanadate completely reversed dexamethasone-induced insulin resistance (by increasing the levels from 9.65 +/- 0.80 to 28.4 +/- 4.9 nmol/h). In cells treated with dexamethasone and insulin, vanadium was partially active and it caused only 30% increase in glycogen synthesis. Exposure of dexamethasone treated cells for 24 h with vanadium did not affect glycogen synthesis. Under identical condition, vanadium had no significant effect in the normal insulin sensitive adipocytes. Vanadium at 100 microM had no effect on 125I-insulin binding to insulin-resistant adipocytes. Glycogen synthesis in the normal and insulin-resistant adipocytes was stimulated by lithium, an inhibitor of glycogen synthase kinase 3 beta, suggesting the involvement of phosphorylation events in dexamethasone-induced insulin resistance.


CONCLUSIONS
Since vanadium was active only in the insulin-resistant adipocytes it is likely that vanadium acts by relieving dexamethasone actions rather than having independent effects. These results provide evidence for the novel insulin sensitizing action of vanadium which might be of future clinical relevance.
Marita
A R
AR
Sir Hurkisondas Nurrotumdas Medical Research Society, Sir H.N. Hospital and Research Centre, Raja Rammohan Roy Road, Mumbai 400 004, India. maritarosalind@hotmail.com
Anilkumar
K L
KL
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002250:Carbon Radioisotopes; D002454:Cell Differentiation; D003907:Dexamethasone / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D051379:Mice; D014638:Vanadates / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D007328:Insulin; D014638:Vanadates; D003907:Dexamethasone; D006003:Glycogen; D008094:Lithium; D005947:Glucose