Increased placental IGF-1/mTOR activity in macrosomia born to women with gestational diabetes

Abstract

Aims: Newborns of women with gestational diabetes mellitus (GDM) are susceptible to be macrosomic, even if the blood glucose levels are in normal ranges. The underlying mechanisms are largely unknown. We tested the hypothesis that placental insulin like growth factor(IGF)-I and mammalian target of rapamycin (mTOR) signaling is activated and amino acid transporter expression is increased in women with GDM who give birth to macrosomic babies.

Methods: 50 Chinese pregnant women with GDM whose blood glucose levels were controlled within normal range were recruited and their placental tissues were collected. 23 women gave birth to macrosomia and 27 women gave birth to babies with normal birth weight. We determined the phosphorylation of key signaling molecules (including Akt, IRS-1, S6K1, 4E-BP-1, and AMPKα) in the placental IGF-I and mTOR signaling pathways. We also measured the protein expression of the amino acid transporter systems A in placenta.

Results: Birth weights (range 2500-4400 g) were positively correlated to maternal IGF-1 (P < 0.05). The activity of placental IGF-I and mTOR signaling was positively correlated (P < 0.05), whereas AMPKα phosphorylation was inversely (P < 0.05) correlated to birth weight. Protein expression of the system A isoform sodium-dependent neutral amino acid transporter (SNAT) 1 were positively correlated to birth weight (P < 0.05).

Conclusions: Up-regulation of placental amino acid transporters may contribute to more macrosomic babies in women with GDM. Activation of IGF-I and mTOR signaling pathways might involve in this effect.

Keywords: Birth weight; Gestational diabetes mellitus; Insulin like growth factor (IGF)-I; Mammalian target of rapamycin (mTOR) signaling; sodium-dependent neutral amino acid transporter (SNAT)1.