The Tyrosine Phosphorylation And Protein Expression Of Insulin Receptor And Insulin Receptor Substrate-1 Are Associated With Skeletal Muscle Insulin Resistance In Gestational Diabetes Mellitus

Objective To investigate the relationship between the tyrosine phosphorylation (TP)and protein expression of insulin receptor(InsR) or insulin receptor substrate-1(IRS-1) in skeletal muscle and insulin resistance in gestational diabetes mellitus(GDM).Methods IRS-1 or InsR expression and TP in skeleton muscle tissue were determined by Western blot and immunoprociptation in women with GDM(GDM group, n=22),normal pregnant women(normal pregnancy group, n=22) and normal nonpregnant women(control group, n=13).Fasting plasma glucose(FPG)and fasting insulin(FINS) were measured by oxidase assay and immunoradioassay. Insulin resistance index were calculated according to homeostasis model assessment(HOMA-IR).Results (1) The levels of FPG, FINS, HOMA-IR (5.61±0.78mmol/L, 15.42±5. 13mU/L, 1.21±0.52) in GDM group were significantly higher than those in normal pregnancy group (4.43±0.46 mmol/L, 10.56±3.07 mU/L, 0.80±0.31) (P＜0.01). The levels of FINS and HOMA-IR in normal pregnancy group were significantly higher than those in control group(7.56±2.31 mU/L,0.47±0.26) (P＜0.01). (2) There were no difference among the level of InsR expression in the three groups(P＞0.05); TP of InsR with insulin stimulation(0.20±0.05)significantly decreased in GDM group, compared with normal pregnancy group(0.26±0.06)(P＜0.01); TP of InsR with insulin stimulation in normal pregnancy group was lower than that in control group(0.31±0.06) (P＜0.01). (3) The level of IRS-1 expression in GDM group (0.64±0.11) was lower than that in normal pregnancy group(0.81±0.13) (P＜0.01); TP of IRS-1 with and without insulin stimulation(0.48±0.14, 0.35±0.12) decreased in GDM group, compared with normal pregnancy group(0.66±0.12, 0.38±0.13) (P＜0.01). TP of IRS-1 with insulin stimulation in normal pregnancy group was lower than that in control group(0.85±0.09) (P＜0.01). (4) TP of InsR with insulin stimulation were negatively related with HOMA-IR in GDM group(r=-0.525, P＜0.01), there were no correlations between protein expression of InsR and HOMA-IR in GDMgroup (r=-0.236, P＞0.05). (5) Protein expression and TP with insulin stimulation of IRS-1 were negatively related with HOMA-IR in GDM group(r=-0.613, -0.632; P＜0.01), TP with insulin stimulation of IRS-1 was negatively related with HOMA-IR in normal prengnacy group(r=-0.526, P＜0.05). Conclusion (1) There is no significant correlation between the protein expression of InsR in skeletal muscle and insulin resistance in GDM, but changes in tyrosine phosphorylation of Insr are associated with insulin resistance in GDM. (2) Changes of protein expression and tyrosine phosphorylation of IRS-1 in skeletal muscle may be one of the molecular mechanisms leading to insulin resistance in patients with GDM.