This article presents information about insulin resistance in women with gestational diabetes and the effect of placental hormones and adipokines in the insulin resistance of pregnancy. It summarises potential mechanisms for the insulin resistance of women with gestational diabetes. During pregnancy insulin sensitivity is quite low in normal women and in women with gestational diabetes. Pregnancy is normaly attended by progressive insulin resistance. The insulin resistance of normal pregnancy is multifactorial, involving the reduced ability of insulin to phosphorylate the insulin receptor, decreased expression of the insulin receptor substrate, and increased levels of the p85a sub-unit of phosphatidylinozitol 3-kinase.
Human placental lactogen and human placental growth hormones increase throughout pregnancy and cause peripheral insulin resistance by increasing the p85a sub-unit of phosphatidylinozitol 3-kinase. Studies in pregnant and non-pregnant women indicate that increases in the p85a subunit of phosphatidylinozitol 3-kinase inhibit its activity and prevent further insulin action.
Adiponectin from adipocites and secreted factors, such as tumor necrosis factor α, are mediators of insulin resistance. Adiponectin stimulates glucose uptake in skeletal muscle. Several studies have demonstrated that adiponectin produced by adipose tissue is significantly lower in women with gestational diabetes than it is in pregnant control women and could be in-
volved in the transition to insulin resistance. Tumor necrosis factor a suppresses mRNA transcription in adipocytes, which might explain the lower levels of serum adiponectin in individuals with gestational diabetes. There is evidence for increased tumor necrosis factor in the skeletal muscle of women with gestational diabetes. Tumor necrosis factor a impairs insulin signaling by increasing serin phosphorilation of the insulin receptor substrate and decreasing the activity of the tyrosine kinase of the insulin receptor.
Serin phosphorylation of the insulin receptor and insulin receptor substrate inhibit insulin action, leading to strong reduced glucose transporter translocation and decreased glucose uptake.
