Effect of vanadate on glycogen synthesis in dexamethasone‐treated 3T3 adipocytes: evidence for a novel insulin sensitizing action

SUMMARYAim  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 n m dexamethasone in the presence or absence of 200 n m insulin for 6 days. Sodium orthovanadate (0–1000 μ m ) was added on day 2 and was present during the last 4 days. At the end, insulin (100 n m ) 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 μ m , 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 μ m had no effect on 125 I‐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 β, 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.