Oral Dexamethasone Precociously Induces Intestinal Fructose Transport In Suckling Rats 570

Abstract

We used intestinal fructose transport as model to determine whether transporters expressed late during development, such as fructose and bile acids, can be reprogrammed to appear earlier. Dietary fructose alone can precociously enhance intestinal fructose transport in weaning (≥ 15 d old) but not in suckling (≤ 14 d old) rats. Dexamethasone (DEX) administration at therapeutic dose (0.4 μg/kg body weight (BW), i.p.) to suckling rats, nonspecifically enhanced all sugar transport, allowed specific induction of fructose transport by luminal fructose but resulted in lower growth rates. We minimized the negative systemic effects of DEX by using a lower dose (0.04μg/kg BW, i.p.) which still nonspecifically enhanced nutrient transport and allowed specific induction of fructose transporters by its substrate. In this study, we determined whether oral administration of low-dose DEX(0.04 μg/kg BW) can result in localized effects and still enhance nutrient transport with little or no reduction in growth rate. DEX was administered orally by gavage to 8 d old pups. On d 8 and 9, high fructose (HF) or high glucose (HG) solutions were fed by gavage at a volume of 2% BW 2X per d as in previous work. Pups stayed with dams at other times then were sacrificed on d 10. Compared to those of controls, same diet-litter mates, non DEX-treated pups (phosphate buffer, orally), in vitro fructose uptake per cm and per mg small intestine increased (p 0.5). There was no statistically significant difference in intestinal lengths (p>0.1, one-way ANOVA) or weights (p>0.8) across all treatment groups. In contrast to i.p. administration, oral DEX, therefore, allows specific induction of fructose transport without nonspecific enhancement of other transport systems. Growth rate, however, still lagged behind controls. Future studies will use lower oral doses of DEX in order to minimize systemic effects on growth rates while maintaining its effects on nutrient transport.