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 （r^2 = 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.

Diabetes pathogenesis and management:the endothelium comes of age

Endothelium,acting as a barrier,protects tissues against factors that provoke insulin resistance and type 2 diabetes and itself responds to the insult of insulin resistance inducers with altered function.Endothelial insulin resistance and vascular dysfunction occur early in the evolution of insulin resistance-related disease,can co-exist with and even contribute to the development of metabolic insulin resistance,and promote vascular complications in those affected.The impact of endothelial insulin resistance and vascular dysfunction varies depending on the blood vessel size and location,resulting in decreased arterial plasticity,increased atherosclerosis and vascular resistance,and decreased tissue perfusion.Women with insulin resistance and diabetes are disproportionately impacted by cardiovascular disease,likely related to differential sex-hormone endothelium effects.Thus,reducing endothelial insulin resistance and improving endothelial function in the conduit arteries may reduce atherosclerotic complications,in the resistance arteries lead to better blood pressure control,and in the microvasculature lead to less microvascular complications and more effective tissue perfusion.Multiple diabetes therapeutic modalities,including medications and exercise training,improve endothelial insulin action and vascular function.This action may delay the onset of type 2 diabetes and/or its complications,making the vascular endothelium an attractive therapeutic target for type 2 diabetes and potentially type 1 diabetes.