Changes in fetal mannose and other carbohydrates induced by a maternal insulin infusion in pregnant sheep

Background: The importance of non-glucose carbohydrates, especially mannose and inositol, for normal development is increasingly recognized. Whether pregnancies complicated by abnormal glucose transfer to the fetus also affect the regulation of non-glucose carbohydrates is unknown. In pregnant sheep, maternal insulin infusions were used to reduce glucose supply to the fetus for both short(2-wk) and long(8-wk) durations to test the hypothesis that a maternal insulin infusion would suppress fetal mannose and inositol concentrations. We also used direct fetal insulin infusions(1-wk hyperinsulinemic-isoglycemic clamp) to determine the relative importance of fetal glucose and insulin for regulating non-glucose carbohydrates.Results: A maternal insulin infusion resulted in lower maternal(50%, P 0.01) and fetal(35-45%, P 0.01) mannose concentrations, which were highly correlated(r2= 0.69, P 0.01). A fetal insulin infusion resulted in a 50% reduction of fetal mannose(P 0.05). Neither maternal nor fetal plasma inositol changed with exogenous insulin infusions.Additionally, maternal insulin infusion resulted in lower fetal sorbitol and fructose(P 0.01).Conclusions: Chronically decreased glucose supply to the fetus as well as fetal hyperinsulinemia both reduce fetal non-glucose carbohydrates. Given the role of these carbohydrates in protein glycosylation and lipid production, more research on their metabolism in pregnancies complicated by abnormal glucose metabolism is clearly warranted.