Treatment of the enhanced intestinal uptake of glucose in diabetic rats with a polyunsaturated fatty acid diet

Intestinal absorption of most nutrients is enhanced in diabetic rats. We wished to test the hypothesis that manipulation of dietary fatty acids will modify enhanced uptake of glucose in rats with established streptozotocin-diabetes. Chow-fed control rats or animals with one week of streptozotocin-diabetes were continued on chow or were fed ad libitum for three weeks with semisynthetic isocaloric diets containing a high content of either essential polyunsaturated or non-essential saturated fatty acids. The jejunal and ileal in vitro uptake of varying concentrations of glucose was much higher in diabetic than control rats fed chow or the saturated fatty acid diet. In contrast, the enhanced uptake of this sugar was reduced or normalized in diabetic rats fed the polyunsaturated fatty acid diet. Feeding the polyunsaturated fatty acid diet was associated with increased brush-border membrane activity of alkaline phosphatase in diabetic jejunum and ileum, but neither the saturated fatty acid diet nor the polyunsaturated fatty acid diet altered brush-border membrane cholesterol or phospholipids in control or in diabetic rats. Mucosal surface area was similar in diabetic rats fed the saturated fatty acid diet or the polyunsaturated fatty acid diet. Thus, (1) feeding the polyunsaturated fatty acid diet diminishes the enhanced jejunal and ileal uptake of glucose in diabetic rats, and (2) the influence of the polyunsaturated fatty acid diet on uptake in diabetic rats was not explained by alterations in intestinal morphology or brush-border membrane content of cholesterol or phospholipids. This study suggests that manipulation of dietary lipids may play a role in the normalization of the enhanced intestinal glucose uptake in rats with established diabetes.     

Evidence for critical-period programming of intestinal transport function: variations in the dietary ratio of polyunsaturated to saturated fatty acids alters ontogeny of the rat intestine

2-week isocaloric modifications in the dietary ratio of polyunsaturated/saturated fatty acids (P/S) alters intestinal transport in rats. This study was undertaken to test the hypotheses that (1) the fatty acid composition of a nutritionally adequate diet in early life has lasting consequences for active and passive intestinal transport processes; and (2) early life feeding experiences with diets of varying fatty acid composition influence the intestines' ability to adaptively up- or down-regulate intestinal transport in later life. Female Sprague-Dawley rats were weaned onto S or P and were maintained on these diets for 2, 10 or 12 weeks. An in vitro uptake technique was used in which the bulk phase was vigorously stirred to reduce the effective resistance of the intestinal unstirred water layer. P decreased and S increased the uptake of glucose, and this effect was progressive from 2 to 12 weeks. Switching from a P to an S diet decreased jejunal but increased ileal uptake of glucose, whereas switching from an S to a P diet was associated with a decline in both the jejunal and the ileal uptake of glucose. The ileal uptake of galactose increased as the animals grew on either P or S. Switching from P to S resulted in a decline in ileal uptake of galactose, whereas the opposite effect was observed when switching from S to P. The effect of feeding P or S on hexose uptake was influenced by the animals' dietary history: ileal glucose and galactose uptake was lower in animals fed P at an early age (PSP) than in animals fed P for the first time in later life (SSP). Jejunal glucose and galactose uptake was also lower in animals fed S at an early age (SPS) than in those fed S for the first time in later life (PPS). The alterations in the uptake of long-chain saturated and unsaturated fatty acids and cholesterol did not progress with longer periods of feeding, and in the jejunum, lipid uptake did not change when switching from P to S or S to P. Early feeding with P (PSP vs. SSP) was associated with lower jejunal uptake of 18:3 and lower ileal uptake of 12:0, whereas previous feeding with S (SPS vs. PPS) was associated with lower ileal uptake of cholesterol. The changes in uptake of hexoses and lipids was not explained by differences in the animals' food consumption, body or intestinal weight or mucosal surface area.(ABSTRACT TRUNCATED AT 400 WORDS)     

Vitamin absorption in the in vivo intestine of normal and infected (Hymenolepis diminuta: Cestoda) rats

Uptake and serosal transfer of the vitamins thiamine, riboflavin and folic acid have been studied in vivo in normal and parasitized rats infected with Hymenolepis diminuta (Cestoda). Regional differences in intestinal uptake of all three vitamins in both uninfected and parasitized animals were not satistically significant. In the parasitized intestine mucosal uptake and serosal transfer of thiamine were significantly inhibited, with increased mucosal accumulation of the vitamin as luminal thiamine concentration increased. Apparent increased riboflavin mucosal uptake in parasitized animals, was not matched by the reduced serosal transfer, suggesting adsorption of the vitamin in the unstirred aqueous layers. Mucosal uptake of folic acid increased in the parasitized gut; serosal transfer and mucosal accumulation were not affected. These results, indicating vitamin malabsorption associated with infection by H. diminuta, are consistent with the parasite inhibiting mucosal passive transport mechanisms. This conclusion is supported by the changes in net water fluxes associated with vitamin uptake in the parasitized intestine.     

Intestinal brush border membrane marker enzymes, lipid composition and villus morphology: effect of fasting and diabetes mellitus in rats

Diabetes mellitus is associated with enhanced passive intestinal uptake of cholesterol and fatty acids. In order to determine the basis for these changes in intestinal permeability, the jejunal morphology and the lipid content of purified brush border membranes (BBM) were measured in fasted and fed control (C) and streptozotocin diabetic (DM) rats. There was no difference between C and DM in BBM sucrase or alkaline phosphatase; fasting had no effect on BBM enzymes in C, but in DM fasting was associated with increased sucrase activity per length of jejunum. In C fasting was associated with higher levels of BBM total phospholipid, lecithin, choline and amine phospholipids, whereas fasting in DM was associated with higher BBM cholesterol and lower free fatty acids. In the fasting DM, there was a greater villus and mucosal surface area than in the fasting C. A previous study demonstrated that with fasting in DM versus C, cholesterol uptake was unchanged, but when animals were fed, cholesterol and fatty acid uptake were greater into the jejunum of fed DM as compared with fed C. In the BBM of fed DM as compared with C, there was a significant increase in total phospholipid, lecithin, phosphatidyl ethanolamine, choline and amine phospholipids, and phospholipid/cholesterol ratio. Thus, (1) fasting is associated with changes in intestinal morphology, BBM lipids; (2) the effect of fasting is different in DM and C; (3) the enhanced uptake of lipids into the jejunum of fed diabetic rats is not due to changes in villus morphology, but may be due to alterations in the BBM phospholipids.     

β-Glucan extracts inhibit the in vitro intestinal uptake of long-chain fatty acids and cholesterol and down-regulate genes involved in lipogenesis and lipid transport in rats

BackgroundDietary fiber reduces the intestinal absorption of nutrients and the blood concentrations of cholesterol and triglycerides.AimWe wished to test the hypothesis that high-viscosity (HV) and low-viscosity preparations of barley and oat β-glucan modify the expression of selected genes of lipid-binding proteins in the intestinal mucosa and reduce the intestinal in vitro uptake of lipids.MethodsFive different β-glucan extracts were separately added to test solutions at concentrations of 0.1–0.5% (wt/wt), and the in vitro intestinal uptake of lipids into the intestine of rats was assessed. An intestinal cell line was used to determine the effect of β-glucan extracts on the expression of intestinal genes involved in lipid metabolism and fatty acid transport.ResultsAll extracts reduced the uptake of 18:2 when the effective resistance of the unstirred water layer was high. When the unstirred layer resistance was low, the HV oat β-glucan extract reduced jejunal 18:2 uptake, while most extracts reduced ileal 18:2 uptake. Ileal 18:0 uptake was reduced by the HV barley extract, while both jejunal and ileal cholesterol uptakes were reduced by the medium-purity HV barley extract. The inhibitory effect of HV barley β-glucan on 18:0 and 18:2 uptake was more pronounced at higher fatty acid concentrations. The expression of genes involved in fatty acid synthesis and cholesterol metabolism was down-regulated with the HV β-glucan extracts. β-Glucan extracts also reduced intestinal fatty-acid-binding protein and fatty acid transport protein 4 mRNA.ConclusionsThe reduced intestinal fatty acid uptake observed with β-glucan is associated with inhibition of genes regulating intestinal uptake and synthesis of lipids. The inhibitory effect of β-glucan on intestinal lipid uptake raises the possibility of their selective use to reduce their intestinal absorption.     

Diets alter jejunal morphology and brush border membrane composition in streptozotocin-diabetic rats

Previous studies have demonstrated enhanced active and passive uptake of many nutrients in animals with experimental diabetes. These changes in absorption cannot be explained by differences in intestinal morphology, although the brush border membrane (BBM) phospholipids do change in diabetes. Manipulation of diet produces alterations in intestinal uptake of lipids and glucose. This study was undertaken to determine the effect of diet and diabetes on jejunal morphology and BBM lipid composition. Rats were rendered hyperglycemic with streptozotocin and were fed for 2 weeks on a diet that was high or low in carbohydrate, essential fatty acids, cholesterol, or protein. In both control and diabetic rats, these diets produced changes in villus height and BBM sucrase and alkaline phosphatase activities. In both control and diabetic rats, BBM phospholipids were unaffected by changes in the dietary content of essential fatty acids, cholesterol, or protein, but total BBM phospholipid content was reduced in animals fed low as compared with high carbohydrate diet. Total BBM phospholipid content was higher in diabetic than in control animals fed the low protein diet, whereas BBM phospholipid content was lower in diabetic than in control animals fed the high carbohydrate diet, and was even lower in diabetic animals fed the low as compared with the high carbohydrate diet. These changes in total phospholipids were due to alterations in the BBM content of phospholipids containing choline. In control animals, BBM cholesterol was higher in rats fed the low as compared with the high cholesterol diet, or the low as compared with the high protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spectrum of effects of dietary long-chain fatty acids on rat intestinal glucose and lipid uptake

Isocaloric modification in the ratio of dietary polyunsaturated-to-saturated fatty acids influences intestinal uptake of actively and passively transported nutrients. This study was undertaken to determine which dietary fatty acid was responsible for these alterations in absorption. Adult female rats were fed isocaloric semisynthetic diets high in palmitic and stearic acids (SFA), oleic acid (OA), linoleic acid (LA), or linolenic acid (LNA). An in vitro technique was used to measure the uptake of varying concentrations of glucose as well as a series of fatty acids and cholesterol. Jejunal uptake of 40 mM glucose was highest in rats fed SFA and lowest in those fed LA; ileal glucose uptake was similar in OA, LA, and LNA, but was lowest in SFA. Jejunal uptake of medium-chain fatty acids (8:0-12:0) was higher in OA than in other diet groups; ileal uptake of medium-chain fatty acids was unaffected by diet. Jejunal and ileal uptake of 18:2 was higher in LNA than in SFA or OA; the uptake of the other long-chain saturated or unsaturated fatty acids was unchanged by diet. The ileal but not the jejunal uptake of cholesterol was increased in LA as compared with SFA or OA, and reduced in LNA as compared with LA. These transport changes were not explained by differences in the animals' food consumption, body weight gain, intestinal mass, or mucosal surface area. We postulate that these diet-induced transport alterations may be mediated via changes in brush border membrane phospholipid fatty acyl composition. Thus, intestinal transport of nutrients may be varied by isocaloric changes in the dietary content of individual fatty acids.     

Feeding rats a diet enriched with saturated fatty acids prevents the inhibitory effects of acute and chronic ethanol exposure on the in vitro uptake of hexoses and lipids

Chow-fed rats were given 15% ethanol in their drinking water for 4 weeks, and then for the next 2 weeks of ethanol exposure they were fed isocaloric semisynthetic diets enriched in either saturated (S) or polyunsaturated (P, linoleic acid) fats. Food intake was lower in ethanol-fed (ETH) than in control (C) rats, but the average body weight gain was similar in ETH and C fed S or P. Intestinal dry weight and the percentage of the intestinal wall comprised of mucosa were more than 2-fold higher in ETH than C fed P, whereas these values were 50% lower in ETH than C fed S. The in vitro jejunal uptake of glucose and galactose was higher in ETH than C fed S, whereas the converse was true when feeding P. These effects were due to differences in the values of the maximal transport rate (Vmax), the Michaelis constant (Km), and the contribution of passive permeation. The relative permeability of the intestine to lipids was unchanged by giving ethanol or by feeding S or P, but the individual rates of uptake of most medium- and long-chain fatty acids and cholesterol were lower in ETH fed P as compared with S. In a second series of studies the acute effect of ethanol exposure was examined: animals were fed S or P for 2 weeks and the intestine was then removed: when 5% ethanol was added directly to the test solutions, there was lower in vitro jejunal and ileal uptake of glucose and higher jejunal uptake of 18:2 when rats were previously fed P, but not in those fed S. In summary; (1) feeding an isocaloric polyunsaturated fatty acid diet has a trophic effect on the intestinal mucosa of animals chronically drinking ethanol; and (2) feeding rats a diet enriched with saturated fatty acids prevents the inhibitory effects of acute and chronic ethanol exposure on the in vitro jejunal uptake of glucose, galactose and lipids observed in animals fed a polyunsaturated diet. Thus, the effect of chronic consumption of ethanol on the active and passive jejunal uptake of nutrients is influenced by the type of lipids in the animal's diet.     

Determinants of intestinal mucosal uptake of short- and medium-chain fatty acids and alcohols

Uptake rates across the jejunal brush border have been measured for water-soluble fatty acids and alcohols and analyzed to determine the relative roles of the unstirred water layer and the lipid cell membrane as determinants of the intestinal absorptive process. Initial studies involving measurement of time courses of electrical transients developed across the intestine exposed to poorly permeant solute molecules showed no anomalous discrimination of probe molecules of different size or charge. This finding suggests that the diffusion barrier in the intestine can be considered as an unstirred water layer. Next, uptake rates of fatty acid were found to be linear with respect to concentration of the test solute, demonstrated no competitive inhibition or contralateral stimulation, had low temperature dependency, and were insensitive to metabolic inhibition, indicating that uptake proceeds by passive diffusion. Passive permeability coefficients, *P, varied from 22 +/- 1.4 to 395 +/- 9.2 nmoles.min(-1).100 mg(-1).mm(-1) for the saturated fatty acids 2:0 through 12:0 and from 119 +/- 3.3 to 581 +/- 45.2 for the saturated alcohols 6:0 through 10:0. Vigorous stirring of the bulk buffer solution enhanced *P values in direct proportion to chain length while the presence of bile acid micelles depressed apparent permeability coefficients in proportion to fatty acid chain length. These results demonstrate that uptake of short-chain fatty acid monomers is rate limited by the lipid cell membrane but diffusion through the unstirred water layer becomes increasingly rate limiting as the chain length increases. It is also possible to conclude from these data that diffusion through the unstirred water layer becomes totally rate limiting for uptake of long-chain fatty acid monomers of physiological importance.     

Amino acid absorption in jejunum of rats in vivo--a kinetic comparison of distal resection effects

Jejunal absorption of leucine and cycloleucine by sham and 50% distal resected rats in vivo was studied by measuring the passive component and the active transport. After 5 months postresection the total amino acid absorption was increased. The mass-transfer coefficients of the passive process (obtained in presence of methionine) were higher in remnant jejunum than that in control rats, whereas the active transport remained unaltered after resection. When the kinetic constants of the saturable and non-saturable components were corrected for the unstirred water layer effects, the "real KD" increased in the resected group, whilst similar values for the "real Km and Jmax" were obtained.     

Thiamine transport in thiamine-deficient rats. Role of the unstirred water layer.

As part of a systematic study of alcoholism and thiamine absorption, the effect of diet-induced thiamine deficiency and the role of the unstirred water layer on the thiamine transport were investigated. Using 3H-labeled dextran as a marker of adherent mucosal volume, jejunal uptake of 14C-labeled thiamine hydrochloride was measured, in vitro, in thiamine-deficient rats and pair-fed controls. Uptake of low thiamine concentrations (0.2 and 0.5 muM) was greater in the thiamine-deficient rats than in the controls. In contrast, uptake rates for high thiamine concentrations (20 and 50 muM) were similar in both groups. While Jmax was unaltered, Km was decreased in thiamine deficiency, suggesting a decrease in unstirred water layer thickness. Accordingly, the thickness of the water layer was measured in both groups of animals and correlated with Jmax and Km under unstirred and stirred conditions. Without stirring, there was no difference in Jmax between the two groups. In contrast, both Km and the water layer were reduced in the thiamine-deficient rats. With stirring, Jmax was not affected, but both Km and the water layer thickness were reduced to similar values in both groups. Reversal of thiamine deficiency resulted in the return of thiamine uptake and the unstirred water layer thickness to control values. These data support the concept of a dual system of thiamine transport and emphasize the role of the unstirred water layer as an important determinant of transport kinetics not only under physiologic situations but also in diet-induced rat thiamine deficiency, a model for a clinical patholigical state. The decrease in the unstirred water layer thickness in thiamine deficiency may be also viewed as a possible adaptive mechanism to facilitate absorption of meager supplies of thiamine.     

Kinetics of uptake of glucose in rabbit jejunum: influence of sodium, unstirred layers, and passive permeation

Failure to account for the effect of the unstirred water layer and the contribution of passive permeation will lead to errors in the estimation of the kinetic constants of glucose uptake into the intestine. It is widely accepted that variations in the concentration of sodium in the bulk phase profoundly influence the rate of uptake of glucose in the intestine, but the kinetic basis for this effect remains in dispute. Accordingly, a previously validated in vitro technique was used to assess the effect of Na+ on the uptake of glucose into rabbit jejunum under conditions selected to reduce the unstirred layer resistance. Varying Na+ had no effect on the uptake of lauryl alcohol and therefore on unstirred layer resistance. The passive permeability coefficient for glucose uptake was estimated from the uptake of L-glucose, of D-glucose at 4 degrees C, or in the presence of 1 mM phlorizin or 40 mM galactose. The permeability for glucose increased as Na+ rose. The values of both the maximal transport rate and the Michaelis constant (Km) were influenced by Na+. A linear relationship was noted between Na+ and the maximal transport rate; the value of Km fell as Na+ was increased to 75 mequiv./L, but Km did not decline further with higher values of Na+. These results support the theoretical predictions of the presence of both an affinity and a velocity effect of the sodium gradient on the intestinal transport system for glucose.     

Characterization of the passive and active transport mechanisms for bile acid uptake into rat isolated intestinal epithelial cells.

The unstirred water layer has been shown to lead to an underestimation of apparent Km (Km(app)) values for active transport processes in intestinal whole tissue preparations. Isolated cells offer several potential advantages in the study of transport processes including a decreased diffusion layer of water adjacent to their absorptive membranes. Initial studies in cells isolated from rat intestine involving measurements of CO2 and lactate production and O2 consumption showed that overall metabolic pathways were functioning. Next, unidirectional uptake rates of bile acids across the isolated cell membrane were determined following correction for extracellular fluid contamination with a non-absorbable marker. Using epithelial cells isolated from jejunum P(app) for eight bile acid monomers varied from 24.9 (taurocholate) to 1563 (deoxycholate) nmol/min/100 mg protein/mM. From these data the incremental free energy changes for the addition of a hydroxyl, glycine and taurine group to the bile acid molecule were calculated to be 982, 1040 and 1464 cal/mol, respectively, values similar to those obtained after correction for unstirred water layer resistance in whole tissue preparations. Following subtraction of the passive component in isolated ileal cells complete kinetic curves for taurocholate and taurodeoxycholate yielded V(app) values of 109 and 70 nmol/min per 100 mg, respectively. Km(app) values of 0.24 mM (taurocholate) and 0.10 mM (taurodeoxycholate) are lower than usually recorded in whole tissue. Bile acid uptake into cells from ileum, but not jejunum, was affected by temperature, metabolic and competitive inhibition. These studies indicate that isolated epithelial cells are a metabolically viable, relatively purified intestinal preparation which discriminates between active and passive transport processes for bile acids under conditions where unstirred water layer artifacts are minimized.     

Intestinal uptake of fatty acids, cholesterol and decanol in ileal resected rabbits: effect of Isocal and Portagen

Isocal, but not Portagen, is associated with increased villus surface area in control rabbits and in animals with an ileal resection. In control animals, Isocal feeding was associated with an increased in vitro jejunal uptake of short and medium-chain length fatty acids and cholesterol, whereas Portagen feeding was associated with a decline in the uptake of short-, medium- and long-chain fatty acids, but an increase in the uptake of cholesterol. In animals with an ileal resection both diets were associated with an increased uptake of long-chain fatty acids and cholesterol. These changes in lipid uptake are not explained by alterations in villus surface area or unstirred water layer resistance.     

Insulin and islet cell transplantation in streptozotocin-diabetic rats: effect on intestinal uptake of hexoses

A previously validated in vitro technique was used to determine the effect of once daily injections of NPH insulin (NPH) and/or islet cell transplantation on the jejunal uptake of 0.5-40 mM glucose and galactose into the jejunum of streptozotocin-diabetic rats. Glucose uptake was greater in untreated diabetic rats than in control animals due to a higher maximal transport rate and a higher passive permeability of the jejunum, and a lower value of the apparent Michaelis constant. Galactose uptake was greater in diabetic rats due to a higher maximal transport rate, but there was also a higher value of the apparent Michaelis constant. This enhanced uptake of glucose and galactose was reduced and normalized by daily injections of NPH insulin or by islet cell transplantation. It is concluded: the jejunal uptake of glucose and galactose is increased in diabetic rats, but the kinetic basis for this change was different for the two sugars; insulin therapy may correct the enhanced uptake of some nutrients in diabetic rats and islet cell transplantation may be at least as effective as exogenous insulin in modifying the intestinal adaptation to diabetes.     

Lack of the intestinal Muc1 mucin impairs cholesterol uptake and absorption but not fatty acid uptake in Muc1-/- mice

Before cholesterol and fatty acid molecules in the small intestinal lumen can interact with their possible transporters for uptake and absorption, they must pass through a diffusion barrier, which may modify the kinetics of nutrient assimilation. This barrier includes an unstirred water layer and a surface mucous coat, which is located at the intestinal lumen-membrane interface. In the present study, we investigated whether disruption of the mucin gene (Muc)1 may influence intestinal uptake and absorption of cholesterol and fatty acid in male Muc1(-/-) mice. The wild-type mice displayed relatively high levels of Muc1, Muc2, Muc3, and Muc4 mRNAs and relatively low levels of Muc5ac and Muc5b mRNAs in the small intestine. The absence of Muc1 mRNA and protein in the small intestines of Muc1(-/-) mice confirmed complete knockout of the Muc1 gene, but the mRNA expression for other mucin genes remained unchanged. Intestinal uptake and absorption of cholesterol but not palmitic acid were significantly reduced in Muc1(-/-) mice compared with the wild-type mice. However, knockout of the Muc1 gene did not impair either expression levels of the genes that encode intestinal sterol efflux transporters Abcg5 and Abcg8 and fatty acid transporter Fatp4 or small intestinal transit rates. We conclude that physiological levels of the epithelial mucin produced by the Muc1 gene are necessary for normal intestinal uptake and absorption of cholesterol in mice. Our study implies that because cholesterol absorption efficiency is reduced by approximately 50% in Muc1-deficient mice, there may be one or more additional pathways for cholesterol absorption.     

Diabetes and intestinal cholesterol uptake from bile salt solutions

A previously validated in vitro technique was used to determine the effect of diabetes mellitus on the intestinal uptake of cholesterol from various micellar bile salt solutions. The bile salts studied included cholic (C), taurocholic (TC), glycocolic (GC), chenodeoxycholic (CDC), taurochenodeoxycholic (TCDC), glycochenodeoxycholic (GCDC), deoxycholic (DC), taurodeoxycholic (TDC), and glycodeoxycholic (GDC). In control rats there was a reciprocal decline in cholesterol uptake with increasing concentrations of these nine bile acids, and cholesterol uptake was greater from the conjugated primary bile acids than from the unconjugated ones. With a 5 mM concentration of bile acids, the ratios of the uptake of 0.2 mM cholesterol in control rats were C = CDC = DC, TCDC greater than TC greater than TDC, and GC = GCDC greater than GDC; with 20 mM concentrations, the ratios of cholesterol uptake in control rats were C greater than CDC greater than DC, TC greater than TCDC greater than TDC, and GC = GCDC greater than GDC. In the diabetic animals cholesterol uptake was higher than in control rats when using 5 or 20 mM of each of the conjugated bile acids and with cholic acid. In contrast, cholesterol uptake was similar in diabetic and control animals when cholesterol was solubilized with 5 or 20 mM CDC or DC. These differences in cholesterol uptake using the various bile acids and the failure of CDC and DC to facilitate the enhanced uptake of cholesterol in diabetic animals remains unexplained.(ABSTRACT TRUNCATED AT 250 WORDS)     

Some properties of the fatty alcohol oxidation system and reconstitution of microsomal oxidation activity in intestinal mucosa

This paper describes the metabolism of fatty alcohols by microsomal and cytosolic fractions from intestinal mucosa. Microsomes of rabbit intestinal mucosa had a high activity of [1-14C]dodecanol oxidation as did those of liver. The intestinal cytosolic fraction also exhibited oxidation activity to a lesser extent than the microsomes did. The reaction product was determined as lauric acid using thin-layer chromatography. Laurylaldehyde was detected as another product, when semicarbazide was added to the incubation system. Cyclodextrins exhibited a stimulation effect similarly to bovine serum albumin on the microsomal activity. We have compared the stimulatory effects of dimethyl-beta-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin and alpha-cyclodextrin, which decrease in that order. Effects of NAD+ and dodecanol concentrations, pH and pyrazole on microsomal activity were compared with those on cytosolic activity. Dodecanol oxidation activity was solubilized and reconstituted with a fatty alcohol dehydrogenase and a fatty aldehyde dehydrogenase separated from the intestinal microsomes. These findings indicate that both the dehydrogenases participate in microsomal oxidation of fatty alcohols to fatty acids with fatty aldehydes as intermediates in the reaction.     

Intestinal uptake of fatty acids and cholesterol in four animals species and man: role of unstirred water layer and bile salt micelle

The uptake (Jd) of fatty acids (FA), fatty alcohols (Alc) and cholesterol (C) into the jejunum of rats (R, Rattus norvegicus), rabbits (RAB, Oryctolagus cuniculus), guinea pigs (GB, Cavia porcellus), and hamsters (H, Mesocricetus auratus) was assessed in vitro. Using jejunal discs the Jd of Alc was H greater than R = GP greater than RAB, the Jd of FA was H-RAB greater than R greater than GP, but the Jd of C was R greater than H greater than RAB greater than GP. The Jd of FA was quantitatively and qualitatively different when using jejunal biopsies; in man the Jd of FA into biopsies was greater than in the other animal species, but there was no difference in Jd of FA into normal human jejunal biopsies and those showing severe abnormalities in villus architecture. There are marked species differences in the passive permeability properties of the jejunum and in the effective resistance of the overlying unstirred water layer, but these differences do not explain the species variations in the uptake of cholesterol.     

Aging: its influence on the intestinal unstirred water layer thickness, surface area, and resistance in the unanesthetized rat

The intestinal absorption of some nutrients changes with aging. As the unstirred water layer (UWL) is an important rate limiting step in the absorption of nutrients in general and of lipid soluble nutrients in particular, we investigated possible changes in the UWL dimensions in the aging rat in vivo. We measured the thickness (d) of the UWL using rapid changes in the luminal sodium concentration to induce changes in the transmucosal potential differences. We assessed the surface area (Sw) and resistance (d/SwD) of the UWL at varying flow rates by using increasingly lipophilic medium chain saturated alcohols as probes. At high UWL resistance, d decreased from 318 to 268 microns between 1 and 29 months of age. As the animals aged, Sw changed from 114 to 106 cm2/100 cm and from 262 to 214 cm2/100 cm at low and high flow rates, respectively, using dodecanol as a probe. The resistance of the UWL (d/SwD) remained relatively stable at all ages studied. These experiments demonstrate that age-related changes in absorption are dependent on the aqueous diffusion coefficient and degree of lipid solubility of the specific nutrients. At low UWL resistance, absorption of compounds with higher diffusion coefficients and greater aqueous solubility is decreased with aging. In contrast, previous studies have demonstrated that the absorption of nutrients with low diffusion coefficients and high lipid solubility increases with aging especially when the resistance of the UWL is high.