University of Leicester
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Studies relating to diabetic pregnancy: Effect of hyperglycaemia upon carbohydrate metabolism and insulin on growth in the rat embryo.

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posted on 2015-11-19, 08:51 authored by James Peregrine. Travers
Congenital abnormalities are up to four times more frequent in diabetic pregnancy than in the general population. Human and animal studies suggest several factors which may be involved in diabetic embryopathy, one of which is maternal hyperglycaemia. Although most clinical studies have reported on insulin treated diabetic pregnancy, (associated with higher serum insulin levels on average), few suggest that lack of insulin as encountered in poorly controlled or undiagnosed metabolically decompensated diabetic pregnancy may contribute to diabetic embryopathy. The first part of this thesis aims to establish whether rat embryos can metabolise excess glucose, (as encountered in maternal hyperglycaemia). Findings have shown that they are unable to do this and it is postulated that the unmetabolized glucose is free to exert any teratological effects. Enzyme kinetic studies show that glucokinase, (active at high glucose concentrations) is inactive during organogenesis. The role of insulin in rat embryonic growth and development was also assessed by culture of rat embryos in insulin deficient rat serum. This showed that embryonic growth and development was abnormal such serum. Supplementation with insulin, restored the ability of the insulin deficient serum to support normal growth and development. Culture of rat embryos in guinea pig serum known to contain a biologically inactive insulin for rat systems also resulted in abnormal rat embryonic growth and development which was largely restored by the supplementation of such serum with a biologically active insulin. Insulin was not detected by sensitive immunocytochemical methods before 13 days gestation. Thus insulin is required for normal embryonic development, but the earliest appearance of rat embryonic insulin was not until the much later stages of organogenesis. This would suggest that the embryo is dependent upon maternal insulin for normal development during most of organogenesis.


Date of award


Author affiliation

College of Medicine, Biological Sciences and Psychology

Awarding institution

University of Leicester

Qualification level

  • Doctoral

Qualification name

  • PhD



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