Different responses to maternal diabetes during the first and second half of gestation in the streptozotocin-treated rat

Abstract

To understand the mechanism of exaggerated hypertriglyceridemia in diabetic pregnancy, streptozotocin-treated rats receiving a daily insulin supplement were mated with normal males and divided into four groups: i) kept under this regime until the 20th day of gestation (DI + II), 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 (DII), 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 beta-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 + II 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 + II rats. Plasma free fatty acid levels were lower in D than in any of the other groups, although they were also lower in DI + II and DI than in C animals. Adipose tissue lipoprotein lipase activity was highest in DI + II animals and their values were very similar to 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.