Dietary fructose vs glucose lowers copper solubility in the digesta in the small intestine of rats

The hypothesis was tested that dietary fructose vs glucose lowers copper solubility in the digesta in the small intestine of rats, which in turn causes a decreased copper absorption. Male rats were fed adequate-copper (5 mg Cu/kg) diets containing either fructose or glucose (709.4 g monosaccharide/kg) for a period of 5 wk. Fructose vs glucose significantly lowered copper concentrations in plasma and the liver, but did not alter hepatic copper mass. Fructose feeding resulted in a significantly lesser intestinal solubility of copper as based on either a smaller soluble fraction of copper in the liquid phase of small intestinal contents or a lower copper concentration in the liquid phase. The latter fructose effect can be explained by the observed fructose-induced increase in volume of liquid phase of intestinal digesta. After administration of a restricted amount of diet extrinsically labeled with⁶⁴Cu, rats fed fructose also had significantly lower soluble⁶⁴Cu fraction in the digesta of the small intestine. Although this study shows that fructose lowered intestinal copper solubility, only a slight reduction of apparent copper absorption was observed. It is suggested that the fructose-induced lowering of copper status in part counteracted the fructose effect on copper absorption at the level of the intestinal lumen.     

Oxygen availability, dietary restriction and transport of glucose 3-O-methylglucose and fructose in the isolated small intestine of rat.

The influences of PO2 of the incubating medium on glucose, 3-O-methylglucose and fructose transport by everted small intestine sacs in semistarved and rats fed ad libitum (controls) was investigated. Moreover fructose uptake and conversion to glucose by intestinal sacs was also studied. The results showed that intestinal sacs from semistarved rats transported larger amounts of glucose and 3-O-methylglucose and took up more fructose than controls, when PO2 of the incubating medium was 150 mm Hg. There was greater fructose conversion to glucose in the intestine of semistarved rats than in controls at all PO2's considered. The greater functional capacity of intestinal tissue of semistarved rats in comparison to controls has been related to larger O2 availability in their intestinal wall.     

Diet-induced epigenetic regulation in vivo of the intestinal fructose transporter Glut5 during development of rat small intestine

Metabolic complications arising from excessive fructose consumption are increasing dramatically even in young children, but little is known about ontogenetic mechanisms regulating Glut5 [glucose transporter 5; encoded by the Slc2a5 (solute carrier family 2 member 5) gene]. Glut5 expression is low postnatally and does not increase, unless luminal fructose and systemic glucocorticoids are present, until ≥ 14 days of age, suggesting substrate-inducible age- and hormone-sensitive regulation. In the present study, we perfused intestines of 10- and 20-day-old rats with either fructose or glucose then analysed the binding of Pol II (RNA polymerase II) and GR (glucocorticoid receptor), as well as acetylation of histones H3 and H4 by chromatin immunoprecipitation. Abundance of Glut5 mRNA increased only with fructose perfusion and age, a pattern that matched that of Pol II binding and histone H3 acetylation to the Glut5 promoter. Although many regions of the Glut5 promoter respond to developmental signals, fewer regions perceive dietary signals. Age- but not fructose-dependent expression of Sglt1 [sodium-dependent glucose co-transporter 1 encoded by the Slc5a1(solute carrier family 5 member 1) gene] also correlated with Pol II binding and histone H3 acetylation. In contrast, G6Pase (glucose-6-phosphatase; encoded by the G6pc gene) expression, which decreases with age and increases with fructose, is associated only with age-dependent changes in histone H4 acetylation. Induction of Glut5 during ontogenetic development appears to be specifically mediated by GR translocation to the nucleus and subsequent binding to the Glut5 promoter, whereas the glucocorticoid-independent regulation of Sglt1 by age was not associated with any GR binding to the Sglt1 promoter.     

Receptors for neurotensin in canine small intestine.

We have previously characterized the neurotensin receptors on the circular smooth muscle (CM) of the canine small intestine (1). In the present studies, using radioligand binding technique, neurotensin receptors were localized on the membranes from deep muscular (DMP) and the submucous plexus while no binding was observed on either the longitudinal smooth muscle or myenteric plexus membranes. The high affinity binding sites (Kd 0.1-0.2 nM) on DMP membranes were similar to those on CM; the low affinity component was of much lower affinity (Kd approximately 40 nM). DMP had 4-6 times higher density of binding sites than the CM. The recognition properties of DMP receptors were similar to those on the CM and reduced sulfhydryl groups were required for the binding activity. The action of neurotensin on the contractility of the canine small intestine, therefore, appears to be through a direct action on the circular smooth muscle and through the prejunctional action on the DMP neurons through distinct receptors. Thiol groups in the neurotensin receptors may be important for the receptor function.     

Fatty-acid chain elongation in rat small intestine.

Microsomal fractions from rat small intestine contain a fatty-acid chain-elongation activity. Cofactor requirements are similar to those of the liver microsomal system, but substrate specificity is different. The polyunsaturated arachidonic and timnodonic acids were elongated at very low rates. These results suggest that the relative contents of specific chain-elongation enzymes are different in liver and small intestine.     

Phosphatidylcholine synthesis in the developing small intestine.

1. Phosphatidylcholine synthesis in the foetal, newborn and adult small intestine of rats was studied by determination of cytidine diphosphocholine-1,2-diacylglycerocholine phosphotransferase (cholinephosphotransferase) and acyl-CoA-1-acyl-sn-glycerol-3-phosphocholine acyltransferase (lysophosphatidylcholine acyltransferase) activities and the incorporation of [1-14C]oleic acid into phosphatidylcholine. 2. Cholinephosphotransferase activity was low in foetal jejunum and ileum, increased 3-4 fold in the ileum by 6 days of age and by 12 days in the jejunum. Jejunal activity remained constant throughout weaning; ileal activity gradually decreased to values 25% of that of the jejunum. 3. Lysophosphatidylcholine acyltransferase activity was high in foetal jejunum and ileum, decreased 70% immediately after birth in the jejunum and increased to adult values by 12 days of age. Ileal activity decreased by 20% after birth, but decreased more rapidly at weaning to 30% of the activity in jejunum. 4. Initial rates and steady-state incorporation of [1-14C]oleic acid into phosphatidylcholine by jejunal rings of 10 day-old rats exceeded that observed in jejunal rings from adult rats by 2-4-fold. 5. In the postnatal jejunum, neither cholinephosphotransferase and lysophosphatidylcholine acyltransferase activities nor oleic acid incorporation were stimulated by cortisone administration in vivo.     

Isoenzymes of glutathione transferase in rat small intestine.

The role of plasminogen activators (PAs) as potential mediators of involution of the rat ventral prostate was investigated by using an approach involving the administration in vivo of anti-PA drugs. The prostates of castrated rats, which had been injected daily for 7 days with the anti-PA drugs 6-aminohexanoic acid, tranexamic acid, aprotinin and cortisol, were assayed for PA activity, weight and cell number. In the prostates from the castrated controls, there was a 10-fold increase in the mean PA activity and a 7-fold decrease in cell number relative to that of the non-castrated animals. Although this rise in enzyme activity could be decreased to some extent by all the drugs except aprotinin, only treatment with high doses of tranexamic acid or cortisol had a statistically significant effect. A similar pattern was observed with respect to the relative potency of the drugs in preventing the loss of prostatic weight and cell number after castration. The effects of cortisol were dose-dependent, with complete inhibition of both the rise in PA activity and cell loss occurring at a dose of about 15 mg/day. Since the concentration of the principal intranuclear androgen, dihydrotestosterone, was the same in the prostates from treated and untreated castrated rats, the effects of cortisol are not due to increased retention of this androgen. Rather, the high inverse correlation (r = 0.86) between the cellular concentration of PA activity and the cell population of the prostate implies that PAs are directly associated with prostatic involution and that cortisol, and to a lesser extent tranexamic acid, blocks the involution process through inhibition of PAs.     

Circadian rhythms in digestive enzymes in the small intestine of rats. I. Patterns of the rhythms in various regions of the small intestine.

The activities of the digestive enzymes, maltase [EC 3.2.1.20], sucrase [EC 3.2.1.26], trehalase [EC 3.2.1.28], Leucine aminopeptidase [EC 3.4.11.1], and alkaline phosphatase [EC 3.1.3.1] were measured in various regions of the small intestine of rats. The activities of all these enzymes were much higher in the jejunum than in the ileum, and in the distal regions of the ileum no sucrase, trehalase or alkaline phosphatase activity was detected. In the jejunum, the activities of all the enzymes tested exhibited clear circadian variations with the highest activity at 0000-0400 h and the lowest at 1200 h when the rats were fed ad libitum. In the ileum, maltase and sucrase also exhibited circadian variations, but the amplitude of the rhythm was smaller than that in the jejenum. Trehalase and alkaline phosphatase did not show any circadian variation in the ileum. Leucine aminopeptidase showed a circadian variation in the ileum with the same amplitude as in the jejunum. The phase of the circadian variations shifted about half a day when the rats were fed in the daytime, but the amplitude of the rhythm did not change.     

Lactate formation by rat small intestine in vitro.

The formation of lactic acid by mucosal slices, rings and muscle from rat jejunum has been studied for periods of up to 8 min. Lactate output by mucosal slices incubated in the absence of glucose was characterised by two phases: a rapid, initial phase of release lasting about 1 min, followed by a much slower phase extending over the remainder of the incubation period. Glucose addition at 30 s initiated a second rapid phase of lactate release into the medium which was again followed by a slower rate of lactate output up to 8 min. The time course of lactate output suggested that there was a negative Pasteur effect in mucosal slices, which could not be reversed by the addition of ADP or glucose 6-phosphate. By contrast, the rate of lactate formation by rings and muscle from rat jejunum increased steadily over the incubation period, indicating a positive Pasteur effect. When Na+ in the incubating medium were replaced by K+, lactate formation by mucosal slices and rings was considerably reduced. Measurements of tissue lactate content before and during incubation revealed that about three-quarters of the lactate released by mucosal slices during the first 30 s of incubation was present initially in the tissue. After the first 30 s the tissue lactate remained constant both in the presence and absence of glucose so that the lactate released into the incubation medium is equivalent to the lactate formed by the slices. The role of the various tissue components of the small intestine in lactate formation is discussed in relation to sites of glucose entry.     

EGTA induced fast potentials in rat small intestine.

Rat small intestine exhibits spontaneous slow-waves and spikes in normal solution. When treated with 0.3 – 0.7 mM EGTA, in calcium free solution, normal rhythmicity disappears and fast rhythmic potentials of duration intermediate to slow-waves and spikes appear. These induced fast potentials are absent in sodium free solution and are eliminated by verapamil, a calcium channel blocker. Application of EGTA to cat, guinea pig, mouse, and toad intestine did not yield fast potentials. The fast potentials appear to result from sodium entering through channels usually used by calcium. The fast potentials may be a phenomena exclusive to rat small intestine.