[Relationship between tyrosine phosphorylation and protein expression of insulin receptor substrate-1 and insulin resistance in gestational diabetes mellitus].
Kata kunci
Abstrak
OBJECTIVE
To study the relationship between tyrosine phosphorylation (TP) and protein expression of insulin receptor substrate-1 (IRS-1) and insulin resistance in patients with gestational diabetes mellitus (GDM).
METHODS
IRS-1 expression and TP in skeleton muscle tissue were determined by Western blot and immunoprecipitation in women with GDM (GDM group, n=22), normal pregnant women (normal pregnancy group, n=22) and normal nonpregnant women (normal nonpregnant group, n=13). Fasting plasma glucose (FPG) and fasting insulin (FINS) were measured by oxidase assay and immunoradioassay.
RESULTS
(1) The levels of FPG, FINS, and insulin resistance index were calculated according to homeostasis model assessment [HOMA-IR; (5.6 +/- 0.8) mmol/L, (15.4 +/- 5.1) mU/L, and 1.2 +/- 0.5] in GDM group were significantly higher than those in normal pregnancy group [(4.4 +/- 0.5) mmol/L, (10.6 +/- 3.1) mU/L, and 0.8 +/- 0.3; P<0.01]. The levels of FINS and HOMA-IR in normal pregnancy group were significantly higher than those in normal nonpregnant group [(7.6 +/- 2.3) mU/L and 0.5 +/- 0.3; P<0.01]. (2) The level of IRS-1 protein expression in GDM group (0.64 +/- 0.11) was lower than that in normal pregnancy group (0.81 +/- 0.13; P<0.01). (3) TP with and without insulin stimulation (0.48 +/- 0.14, and 0.35 +/- 0.12) decreased in GDM group, compared with normal pregnancy group (0.66 +/- 0.12, and 0.38 +/- 0.13; P<0.01). TP with insulin stimulation in normal pregnancy group was lower than that in normal nonpregnant group (0.85 +/- 0.09; P<0.01). (4) Protein expression and TP with insulin stimulation of IRS-1 was negatively related to HOMA-IR in GDM group (r=- 0.613, -0.632; P<0.01), and TP with insulin stimulation was negatively related to HOMA-IR in normal pregnancy group (r=-0.526, P<0.05).
CONCLUSIONS
Changes in 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.
