Elmer S David

Luminal fructose modulates fructose transport and GLUT-5 expression in small intestine of weaning rats

In neonatal rats, precocious introduction of dietary fructose significantly enhances brush-border fructose transport rates and GLUT-5 mRNA levels during early weaning. In this study, these rates and levels were more than two times higher in the anastomosed intestine compared with those in the bypassed loop of weaning pups that underwent Thiry-Vella surgery and consumed high-fructose (HF) diets. In Thiry-Vella pups fed fructose-free (NF) diets, uptake rates and mRNA levels in the anastomosed intestine were very low and similar to those in the bypassed loop. In sham-operated littermates, transport rates and mRNA levels were similar between intestinal regions that corresponded to anastomosed and bypassed loops in Thiry-Vella pups and were two to three times greater in pups fed HF than in those fed NF diet. In contrast, rates of brush-border glucose transport and levels of SGLT-1 and of GLUT-2 mRNA were independent of diet and were similar between bypassed and anastomosed regions. Changes in GLUT-5 expression did not follow a distinct diurnal rhythm. When pups were fed HF diet after 12 h of starvation to empty the intestinal lumen, fructose transport rates increased with feeding duration and reached a plateau 12-24 h after feeding; in contrast, GLUT-5 mRNA levels were highest within 4 h after arrival of chyme in the jejunum and then decreased gradually and returned to baseline levels 24 h later. In littermates fed NF diet, mRNA levels and uptake rates were each independent of feeding duration. Luminal, and not endocrine, signals regulate GLUT-5 expression in weaning pups.

Dietary Induction of Intestinal Fructose Absorption in Weaning Rats

ABSTRACT: The onset of developmentally induced changes in rat intestinal nutrient absorption is well known: brushborder glucose and fructose transporters appear during prenatal and postweaning periods, respectively. The onset of diet-induced regulation, however, is unknown. To test the hypothesis that intestinal glucose and fructose transport is regulated by diet during weaning and postweaning, we fed rats experimental diets containing high (65%) glucose, high fructose, high sucrose, or no carbohydrate. In 16-d-old rats, 6 d of dietary fructose but not glucose modestly increased fructose absorption in everted sleeves of small intestine (SI) over control (mother-fed with access to chow) rats (p = 0.02). In 21-d-old (age when sucrase is present) rats, dietary fructose and sucrose each dramatically enhanced (p = 0.004) fructose absorption over control rats and rats fed high glucose or carbohydrate-free diets. In 35− (postweaning) and 60-d-old rats, dietary fructose and sucrose, but not glucose, stimulated fructose absorption (p < 0.005) over rats fed a carbohydrate-free diet. In all age groups, intestinal glucose absorption was independent of diet (p ≥ 0.12), and experimental rats grew at the same rate as control rats. Absorption of fructose or glucose was 2–3 times greater in the proximal and middle than in the distal SI. Intestinal fructose, but not glucose, absorption can be induced by diet even during early weaning, and dietary fructose followed by sucrose is the most potent inducer. Thus, mechanisms of diet regulation can change ontogenetically, and early introduction of certain diets can induce appearance of certain nutrient transporters.

Ontogenetic development of rat intestinal bile acid transport requires thyroxine but not corticosterone.

Absorption of bile acids by the distal ileum is an essential component of the enterohepatic circulation. In neonatal rats, the appearance of the apical sodium-dependent bile acid transporter (ASBT) at 17 d of age coincides with increases in serum corticosterone and thyroxine. We tested the hypothesis that these hormones modulate ASBT expression during ileal development. Taurocholate uptake into the isolated ileum of normal 20-d-old pups exhibited saturable (Km = 0.52 mM, Jmax = 0.34 pmol mg/min) and nonsaturable (Kdiff = 0.015 min−1) components and was two to five times greater than uptake in the proximal intestine. Hypothyroid or euthyroid pups received daily thyroxine injections starting at 6 d of age. At 12 d of age, serum concentrations of thyroxine, ileal abundance of ASBT mRNA, and ileal rates of taurocholate uptake were low in hypothyroid pups that received an injection of vehicle (HT−) or thyroxine (HT+) and in euthyroid pups that received an injection of vehicle (ET−) or thyroxine (ET+). At 20 and 26 d, ileal ASBT mRNA abundance and taurocholate uptake rate remained low in HT− pups but increased dramatically in ET− and ET+ pups, paralleling the increase in serum thyroxine. Restoration of normal plasma thyroxine in HT− pups by thyroxine injections (HT+) restored normal ASBT development. Sodium-glucose co-transporter activity and mRNA expression were independent of serum thyroxine levels. Corticosterone levels were significantly lower in pups that were adrenalectomized at 10 d of age. ASBT mRNA abundance and taurocholate uptake rate increased markedly with age but were the same in adrenalectomized, sham-operated, and nonoperated pups. Hence, endogenous thyroxine but not corticosterone regulates the developmentally timed appearance of ASBT.

Age-Dependent Modulation of Intestinal Nutrient Transport by Dexamethasone in Neonatal Rats

Age-Dependent Modulation of Intestinal Nutrient Transport by Dexamethasone in Neonatal Rats

Oral Dexamethasone Precociously Induces Intestinal Fructose Transport In Suckling Rats 570

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.

Precocious Induction of Intestinal Fructose Transport with Low-Dose Dexamethasone in Suckling Rats † 1509

Precocious Induction of Intestinal Fructose Transport with Low-Dose Dexamethasone in Suckling Rats † 1509

DEXAMETHASONE PRECOCIOUSLY INDUCES INTESTINAL SUGAR TRANSPORT IN SUCKLING RATS |[dagger]| 474

During normal development, intestinal fructose transport is enhanced only in postweaning (>28d) rats. Early introduction of a high fructose diet enhances fructose absorption in weaning (14-28d) but not in suckling (<14d) rats. In contrast, glucose absorption is independent of diet in both weaning and suckling stages. In this study, we determined whether Dexamethasone (DEX) would allow dietary induction of sugar transport in suckling rats. DEX, 0.4ug/g body weight (BW), was administered i.p. once daily to rat pups from d 5-9. Pups were gavage-fed on d 8-9 with sugar solutions containing high fructose (HF) and high glucose (HG) at a volume of 2% BW 2X per d. Pups stayed with dams at all other times. Control litter mates were fed similar solutions but received phosphate buffer i.p. instead of DEX. On d 10, pups were sacrificed and intestinal uptake studies using the everted sleeve technique were performed. Two-way analysis of variance (ANOVA) showed that fructose uptake increased 3X in DEX-treated pups fed HF (P<0.0001) but only 2X in DEX-treated pups fed HG (P<0.0001) over control. There was also a 2X significant increase in glucose uptake in DEX-treated pups fed HG(P<0.0001) and HF (P<0.0001). Uptakes were 2-3X greater in the proximal and middle than in the distal small intestine. DEX-treated pups failed to gain weight compared to control (P<0.0001). There was no statistically significant difference in intestinal lengths and weights across treatment groups. DEX therefore non-specifically enhances transport of nutrients and also allows specific induction of fructose transporters by its substrate. The proximate mechanism of this DEX effect remains unclear and is a subject of future research.

EFFECT OF DEXAMETHASONE ON INTESTINAL SUGAR UPTAKE CAPACITY IN SUCKLING RATS.† 1367

Dexamethasone (DEX) is a glucocorticoid that is now widely used not only to prevent the development of bronchopulmonary dysplasia but also to facilitate weaning of infants already with BPD from respirator support. Concerns about its usage have mainly been related to sepsis, hypertension, hyperglycemia and delayed weight gain. The aim of this study is to address the latter complication and relate DEXs effect on small intestinal sugar uptake capacity. DEX, 0.4ug/g body weight (BW), was administered i.p. once daily to rat pups from d 8-9 (Group I). Control litter mates received phosphate buffer i.p. instead of DEX (Group II). Pups stayed with dams at all times. On d 10, pups were sacrificed and intestinal uptake studies using the everted sleeve technique were performed. DEX-treated pups failed to gain weight compared to control (P<0.0001). There was no statistically significant difference in small intestinal (SI) lengths (P=0.8) and weights (P=0.3) across treatment groups. One-way analysis of variance (ANOVA) showed that intestinal glucose uptake capacity increased 2X in DEX-treated pups (P<0.05) and intestinal fructose uptake capacity increased 3X in DEX-treated pups (P<0.03) over control. Two-way ANOVA showed that intestinal glucose uptake per mg and per cm SI doubled (P=0.003; P=0.003) while intestinal fructose uptake per mg and per cm SI tripled (P<0.0001; P=0.0006) in DEX-treated pups over control. These magnitudes of increases in sugar uptake was evident across intestinal regions. Uptakes were 2-3X greater in the proximal and middle than in the distal SI. DEX therefore non-specifically enhances intestinal transport of sugars and possibly other nutrients but these effects do not make up for its catabolic effects and prevent decrease in somatic growth. The proximate mechanism of DEXs effect on intestinal sugar uptake remains to be elucidated.