Modifications induced by gestational diabetes mellitus on cellular membrane properties

Abstract

Alterations in erythrocyte plasma membrane properties (enzymatic activities and membrane fluidity) have been observed in patients affected by insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). In order to verify whether these alterations are present also in gestational diabetes mellitus (GDM) we studied the plasma membranes obtained from two different cellular types (erythrocyte from both mother and cord blood and placenta syncytiothrophoblast cell) of 16 healthy pregnant women and 15 women affected by GDM. The following determinations were performed on the membrane preparations: Na+/K(+)-ATPase activity, acetyl-cholinesterase (AchE) activity, membrane fluidity and cholesterol:phospholipid ratio. We observed a reduction of both enzymatic activities and a decrease of membrane fluidity in maternal and cord blood erythrocytes and in syncytiotrophoblast plasma membranes in GDM pregnant women in comparison with controls. The cholesterol to phospholipid ratio was significantly lower in the erythrocyte membranes of women affected by GDM than in normal pregnant women, while it was increased in the cord blood erythrocyte membranes and in placental membranes in GDM in comparison with controls. The present study found, in GDM patients, a membrane alteration similar to the abnormality reported in IDDM and NIDDM (i.e. decreased Na+/K(+)-ATPase activity), while opposite modifications were observed with regard to other membrane activities and properties. The different membrane alterations observed in GDM with respect to IDDM and NIDDM might be linked to the different degree of metabolic control, on the contrary the reduced Na+/K(+)-ATPase activity might be a primary event in the pathogenesis of diabetes mellitus per se and might constitute a signal of high risk of developing the disease later in the women affected by GDM during pregnancy.

Mitochondrial content, oxidative, and nitrosative stress in human full-term placentas with gestational diabetes mellitus

“…Our data show that GDM placentas have higher AMPK levels compared with the control placentas, whereas the COX4 levels and ATPase activity are similar between both groups. It is important to take into account that the activity that we determined represents the activity of all the ATPase in the placenta, and specifically the Na+/K(+)-ATPase activity was reduced in placental syncytiotrophoblast cells of GDM patients [27]. Is has been described that AMPK is a key for signaling kinases to induce GLUT4 expression and to increase glucose uptake in muscles [28], whereas the complex IV activity has been closely associated with mitochondrial oxidative phosphorylation capacity [29].…”

Fetal erythrocyte membrane lipids modification: preliminary observation of an early sign of compromised insulin sensitivity in offspring of gestational diabetic women

“…Whether the ratio of insulin to plasma glucose manipulates the fatty acid transport process in gestational diabetes is unknown. However, modification of membrane properties such as Na+/K+ ATPase activities and reorganization of membrane cholesterol and phospholipids has been reported in erythrocytes and placenta from gestational diabetes [30]. More recently, it has been reported that expression of the genes for fatty acid transport was up‐regulated, whilst genes for lipoprotein lipase were down‐regulated in the placenta of women with gestational diabetes [31].…”

Effects of gestational diabetes on human placental glucose uptake, transfer, and utilisation

“…Other characteristics of GDM placentae possibly cause reduced nonfacilitated diffusion. For example, placentae from GDM pregnancies have been shown to have increased cytotrophoblastic cell numbers, thickening of the basement membrane and reduced vascularisation of the villi [20,21], as well as reduced syncytiotrophoblast membrane fluidity and increased cholesterol content [37]. One study found a 35 to 45 % reduction in uteroplacental blood flow in diabetic pregnancies and the authors suggested this was due to a reduced intravillous space [38].…”