PLACENTAL GLUCOSE TRANSPORTER (GLUT 1) IN FETAL SHEEP IS REGULATED BY TIME-DEPENDENT CHANGES IN GLUCOSE AND INSULIN CONCENTRATIONS. ▴ 1828

Abstract

Fetal glucose supply under basal conditions is solely derived from the maternal circulation via placental transport. Placental glucose transport is mediated by facilitative glucose transporters, the predominant isoform being Glut 1. We examined the time-dependent effect of maternal glucose(HYPERglycemic) and insulin (HYPOglycemic) infusions on placental Glut 1 in late gestation chronically catheterized pregnant sheep. HYPER (+80% normal; n=14) was produced by maternal continuous infusions of 50% glucose and HYPO( 48hr-41d) and hypoglycemia (<50%) with consistent fetal hypoinsulinemia, respectively. Placental tissue was analyzed for Glut 1 levels(50-55 kD) at these different time points by quantitative Western blot analysis using a rabbit anti-rat Glut 1 COOH IgG. HYPER caused a transient but minimal increase in Glut 1 protein levels at 2-3 hr (p<0.05) followed by a normalization between the 10 and 20d duration. In contrast, HYPO led to a 50% decline starting at 24-48 hr and lasting through 25 to 41d (p<0.05). We conclude that 1] changes in placental Glut 1 are time-dependent, and 2] HYPER causes a transient but minimal increase while HYPO leads to a persistent decline in placental Glut 1 concentrations. We speculate to the extent that changes in placental glucose transporter characteristics influence the rate of maternal-fetal glucose transport & fetal glucose availability, the HYPO induced decline in placental Glut 1 may mediate the development of fetal hypoglycemia and concomitant intra-uterine growth restriction.