Vanadate enhances but does not normalize glucose transport and insulin receptor phosphorylation in skeletal muscle from obese women with gestational diabetes mellitus

OBJECTIVE: We compared the insulin-mimetic effects of vanadate, a protein-t yrosine phosphatase inhibitor, with the effects of insulin on skeletal musc le glucose transport and insulin receptor and insulin receptor substrate 1 phosphorylation to test the hypothesis that protein-tyrosine phosphatases p articipate in pregnancy-induced insulin resistance. STUDY DESIGN: Skeletal muscle fiber strips were obtained from the rectus ab dominis during cesarean delivery in 7 patients with gestational diabetes me llitus, 11 pregnant women with normal glucose tolerance (pregnant control g roup), and 11 nonpregnant women undergoing elective surgery (nonpregnant co ntrol group). Muscle tissues were incubated in vitro for 15 to 60 minutes w ith or without maximal insulin (100 nmol/L) or sodium vanadate (6 mu mol/L) . Insulin receptor and insulin receptor substrate 1 tyrosine phosphorylatio n were measured, as was 2-deoxyglucose transport. The levels of protein-tyr osine phosphatase 1B were measured by Western blot analysis. RESULTS: Vanadate stimulated maximal 2-deoxyglucose transport more than did insulin alone in all samples (P < .05), but the value was still less in mu scle tissues from pregnant control subjects and patients with gestational d iabetes mellitus (P < .05). In muscle tissues from pregnant control subject s vanadate increased tyrosine phosphorylation oi the insulin receptor and i nsulin receptor substrate 1 to levels similar to those in muscle tissues fr om nonpregnant control subjects. In patients with gestational diabetes mell itus vanadate increased insulin receptor and insulin receptor substrate 1 t yrosine phosphorylation, but these values remained less than in muscle tiss ues from nonpregnant control subjects (P < .05). Protein-tyrosine phosphata se 1B levels were not significantly different in skeletal muscles from each group. CONCLUSION: Vanadate did not restore normal glucose transport activity duri ng pregnancy complicated by gestational diabetes mellitus, which indicates that decreased glucose uptake is probably not caused by impaired tyrosine p hosphorylation events alone. Increased serine kinase activity and impaired glucose transporter 4 translocation probably contribute to insulin signalin g abnormalities associated with pregnancy, especially in patients with gest ational diabetes mellitus.