1. Investigación

To understand the mechanism of exaggerated hypertriglyceridemia in diabetic pregnancy, streptozotocin-treated rats receiving a daily insulin supplement were mated with nom1al males and divided into four groups: i) kept under this regime until the 20th day of gestation (Dl+ll), ii) the same regime until the 12th day of gestation (DI), iii) the insulin treatment was suspended during the first half of gestation (days 0-12) and then restored on a daily basis until the 20th day (DU), and iv) no insulin treatment was given after mating (D). All animals were studied on day 20. Despite increased food intake, maternal conceptus-free body weight was greatly reduced in the D animals as compared with the other groups whose values did not differ. Both the plasma glucose and ~-hydroxybutyrate levels were increased more in D than in DI rats and values in both groups were greater than in the others. Insulin levels showed an opposite trend to that of glucose, but the values in DI+ll rats were higher than in untreated intact control rats (C). The plasma triglyceride concentration was highest in the DI rats, followed by the D group whose values were still significantly higher than in either C or DI+ll rats. Plasma free fatty acid levels were lower in D than in any of the other groups, although they were also lower in Dl+II and DI than in C animals. Adipose tissue lipoprotein lipase activity wa~ highest in DI+II animals and their values were very similar lo those found in DII, whereas the values in the C, D and DI animals were all similar and much lower. Results indicate that reductions in fat accumulation during the first half of gestation impair the activation of lipolytic activity in the severe diabetic mother during late gestation. During this period lipolysis helps sustain maximal hypertriglyceridemia, which develops in animals whose diabetes was circumscribed to the second half of gestation. In general, our findings show that anabolic changes during the first half of gestation affect metabolic events during late gestation.

To determine whether changes in uterine blood flow affect placental glucose transfer in the diabetic pregnant rat, on the 7th day of gestation rats were intravenously treated with either streptozotocin (45 mg/kg) (diabetics) or buffer (controls). On the 20th day of gestation, fetal body weight and uterine blood flow appeared reduced whereas fetal/maternal plasma glucose was enhanced and lactate ratios were unchanged in diabetics versus controls. After 20 min of (U- 14C)-D-glucose infusion through the maternal left uterine artery, plasma values of fetuses from left and right uterine horns were higher for 14C-glucose and lower for 14C-lactate in diabetics versus controls, and placental glucose transfer was greatly augmented in diabetics whether or not uterine blood flow was included in its calculation. Whereas a linear correlation existed between placental glucose transfer and maternal plasma glucose concentration, transferred glucose conversion into lactate remained stable even when the maternal glucose level was high. It was concluded that enhanced placental glucose transfer in the pregnant diabetic rat is not modified by reduced uterine blood flow. The limited capacity of the fetus to handle the great incoming flux of glucose through the placenta of a severely diabetic mother produces permanent hyperglycemia which may impair fetal growth.