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During pregnancy, the developing fetus is dependent on its mother for all nutritional requirements. It is not surprising, therefore, that variations in maternal nutrition can be reflected in alterations in fetal health and well-being. Interestingly, the changes can persist into adulthood and may result in increased risk of diseases such as diabetes, obesity and cardiovascular disease. The first observations of these phenomena resulted in the development of hypotheses collectively brought under the heading of "fetal" or, more recently, "developmental" programming. In this review, we will examine some of the animal models used to understand the mechanisms involved and attempt to determine whether there are common, "gatekeeper", pathways or genes, altered by the different nutritional stresses. We will concentrate primarily on nutrition related to post-natal development of hypertension and will restrict the review to studies in rodents, since that is where most of the mechanistic studies are being undertaken. Our conclusions are that, while there may well be some common gatekeeper pathways, there is also some diversity of mechanism which may contribute to the generation of the same or similar phenotypes.

The present investigation was undertaken to characterize the direct inhibitory action of the peroxyvanadium compounds oxodiperoxo(1, 10-phenanthroline) vanadate(V) (bpV(phen)) and oxodiperoxo(pyridine-2-carboxylate) vanadate(V) (bpV(pic)) on pig microsomal glucose-6-phosphatase (G-6-Pase) activity and on glucagon stimulated hyperglycemia in vivo. Both bpV(phen) and bpV(pic) were found to be potent competitive inhibitors of G-6-Pase with Ki values of 0.96 and 0.42 microM (intact microsomes) and 0.50 and 0.21 microM (detergent-disrupted microsomes). The corresponding values for ortho-vanadate were 20.3 and 20.0 microM. Administration of bpV(phen) to postprandial rats did not affect the basal glucose level although a modest and dose-dependent increase in plasma lactate levels was seen. Injection of glucagon raised the plasma glucose level from 5.5 mM to about 7.5 mM in control animals and this increase could be prevented dose-dependently by bpV(phen). The inhibition of the glucagon-mediated blood glucose increase was accompanied by a dose-dependent increase in plasma lactate levels from 2 mM to about 11 mM. In conclusion, the finding that vanadate and bpV compounds are potent inhibitors of G-6-Pase suggests that the blood-glucose-lowering effect of these compounds which is seen in diabetic animals may be partly explained by a direct effect on this enzyme rather than, as presently thought, being the result of inhibition of phosphoprotein tyrosine phosphatases and thereby insulin receptor dephosphorylation., (Copyright 1999 Academic Press.)