The Effects of Diabetes on Placental Lipase Activity in the Rat and Human

Abstract

ABSTRACT. Lipase activities were measured at pH 4 and properties of lipoprotein lipase (6,7), whereas a second, measured pH 8 in the placentas of rats made diabetic by streptozo-at pH 4, is probably lysosomal in origin (8). tocin treatment and also in the placentas of women classiLipoprotein lipase activity in adipose tissue and diaphragm fied as having 1) impaired glucose tolerance or type 2 was found to be reduced in streptozotocin-induced diabetic rats, diabetes, 2) type 1 diabetes with no associated vascular but in the same experiments the lipoprotein lipase-like activity complication, and 3) type 1 diabetes with associated vas-in the placenta was unaffected (9, 10). However, Shafrir and cular disease. In both sets of experiments, the placentas coworkers (4, 9) showed that lipolytic activity in the placentas of were compared with normal control groups. The placental diabetic rats was increased, and they inferred that this was due lipase activity measured at pH 8 was not significantly to an increase in placental "intracellular" lipase activity. Theredifferent in either streptozotocin-treated rats or impaired fore, in the study reported here, we tested the hypothesis that glucose toleranceldiabetic women as compared with con-placental pH 4 lipase activity is increased in the placentas of trols, whereas the lipase activity measured at pH 4 in-diabetic women and rats. We have measured both the pH 8 creased significantly as compared with controls in both lipase and the pH 4 lipase activity in the placentas of streptozospecies. Furthermore, in the women there was a significant tocin-induced diabetic rats and also in the placentas of mothers correlation between placental lipase activity at pH 4 and who were classified as having IGT or type 2 diabetes and those birth weight in impaired glucose tolerance/type 2 diabetes. classified as having type 1 diabetes with or without vascular It is suggested that the increased placental lipase activity disease. may contribute to the increased fetal weight in human diabetic pregnancy, by contributing to the increased fat Chemicals and isotopes. 3H-9-10 trioleyl glycerol (sp act 0.5-1.0 Ci/mmol) was purchased from Amersham International plc Abbreviations (Bucks, UK). Phosphatidylcholine, 9-10 trioleyl glycerol (99%) glycerol, and BSA were all purchased from Sigma Chemical IGT, impaired glucose tolerance Company (Dorset, UK). Heat-inactivated horse serum was purchased from Flow Laboratories (Herts, UK). Streptozotocin was kindly provided by Dr. N. MacLeod (The UpJohn Co., Kalamazoo, MI). Other chemicals were ANALAR grade, purchased Diabetes in pregnancy produces major changes in maternal from BDH (Poole, UK). plasma lipid concentrations (1-3). Plasma triglycerides are ele- Streptozotocin-induced diabetes in rats.Female CSE Wistar vated in both type 2 diabetes and gestational diabetes, whereas rats were made diabetic before mating by a single i.v. adminisin type 1 diabetic patients plasma triglycerides are not signifi-tration of 40 mg/kg of streptozotocin (1 1). Serum glucose was c...

Glucose Suppression of Insulin Secretion in Chronically Hyperglycemic Fetal Sheep

“…The present studies provide evidence, therefore, that hyperglycem ic suppression of fetal insulin secretion also has the potenti al to limit an increase in the rate of fetal growth in spite of hyperglycemia. By extrapolation, it also is possible that such a mechanism, if operative in human fetuses, could to help explain part of the variation in fetal we ight among diabetic pregnancies and the reduction in fetal weight that has been observed in pregnancies of some wom en with more severe and long-standing cases of diabetes mellitu s (31)(32)(33), as well as a relatively lesser degree of fetal macrosomia at term among pregnant women with insulin-dependent diabetes comp ared with gestational diabetics (34).…”

Fatty Acid Supply to the Human Fetus

“…The human placental microvillous membrane contains specific binding sites for the lipoproteins (very-low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein), which transport TGs and other esterified lipids (34,111,144). The presence of lipase activity in the placenta (7,79,121,125) allows the production of NEFA from TG. The relative contribution of circulating NEFA and TG to total placental flux in human pregnancy is not known, although isotope studies in guinea pigs indicate that more of the fatty acid in the fetal circulation is obtained from maternal TG than from circulating NEFA (129).…”

Effect of placental function on fatty acid requirements during pregnancy

“…The human placental microvillous membrane contains specific binding sites for the lipoporoteins (VLDL, LDL and HDL), which transport TG and other esterified lipid (Cummings et al, 1982;Naoum et al, 1987;Wittmaack et al, 1995). The presence of lipoprotein lipase activity (Rothwell & Elphick, 1982;Shafrir & Barash, 1987;Kaminsky et al, 1991;Bonet et al, 1992) allows the production of NEFA from TG. The relative contribution of NEFA and TG to total placental flux in human pregnancy is not known, although isotope studies in guinea-pigs indicate that more of the fatty acid in the fetal circulation is obtained from maternal TG than NEFA (Thomas & Lowy, 1987).…”