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PubMed2004

Sorbitol prevents the self-aggregation of unfolded lysozyme leading to and up to 13 degrees C stabilisation of the folded form.

We present a calorimetric investigation of stabilisation of hen egg-white lysozyme with sorbitol in the pH range 3.8-10.5. Differential scanning calorimetry and steady-state fluorescence were used to determine the denaturation temperatures of lysozyme as a function of sorbitol concentration. The fluorescence data were collected in the presence of 2M urea to lower the melting point of the protein to an observable range of the instrument. The effect of sorbitol on the activation energy of unfolding was investigated by scanrate studies. The effect of sorbitol lysozyme interaction was investigated using isothermal titration calorimetry. The titration experiments were performed with folded as well as unfolded lysozyme to investigate in more detail the nature of the interaction. The data obtained in those experiments show a remarkable stabilisation effect of sorbitol. We observed a 4.0 degrees C increase in the Tm for 1 M sorbitol in the pH range 3.8-8.5 by scanning calorimetry. The effect increases dramatically at pH 9.5 where we observe a 9.5 degrees C stabilisation. An increase in the sorbitol concentration to 2 M stabilises lysozyme by 11.3-13.4 degrees C in the pH range 9.5-10.5. In the absence of urea, no significant effects of sorbitol were observed on the activation energy for unfolding for lysozyme at pH 4.5. This indicates together with the results from the titration experiments that sorbitol may stabilise the folded form of lysozyme by destabilising the unfolded form of lysozyme. At pH values at and above lysozyme's pI (approximately 9.3), the unfolding of the protein is accompanied with a substantial amount of self-aggregation seen in the calorimetry experiments in the ratio of DeltaH(cal)/DeltaH(vH). In the presence of sorbitol, the self-aggregation was counterbalanced by higher sorbitol concentrations. These results strongly suggest a negative influence of sorbitol on the unfolded form of lysozyme and thereby stabilising the native form.

Calorimetry, Differential Scanning↗
PubMed1985

H7 antiserum-sorbitol fermentation medium: a single tube screening medium for detecting Escherichia coli O157:H7 associated with hemorrhagic colitis.

Escherichia coli serotype O157:H7 has been isolated from outbreaks and sporadic cases of hemorrhagic colitis. There is convincing evidence that it can cause this diarrheal disease. Because of the interest in hemorrhagic colitis, it has become desirable to detect this particular strain in human feces, which usually contains many other strains of E. coli. Two characteristics of the incriminated E. coli O157:H7 strain have made its isolation and identification easier. It does not ferment D-sorbitol rapidly, in contrast to about 95% of other E. coli strains. In addition, the strain has H antigen 7, but only about 10% of other E. coli strains have this particular antigen. To screen for E. coli O157:H7 we devised H7 antiserum-sorbitol fermentation medium (18 g of enteric fermentation base, 10 g of D-sorbitol, 4 g of agar, 10 ml of Andrade indicator, 989 ml of water; all ingredients were mixed, autoclaved, and cooled; 1 ml of E. coli H7 antiserum was then added). Colonies to be screened were inoculated into this medium. Strains of E. coli O157:H7 gave a characteristic pattern; they did not ferment sorbitol and were immobilized in the semisolid medium because of the reaction of their flagella with the flagella antiserum. Almost all other strains of E. coli gave a different pattern; they fermented sorbitol or were not immobilized by the H7 serum or both. Strains which were presumptive positives (sorbitol negative, H7 positive) were then tested in E. coli O157 serum by slide or tube agglutination. The number of strains which were presumptive positive by H7-sorbitol medium but then were not found to be O157 was less than 1%. A second approach has been helpful in deciding which colonies to screen in H7-sorbitol medium. MacConkey-sorbitol agar (22.2 g MacConkey agar base [which contains no sugar], 10 g of D-sorbitol, 1,000 ml of water) was designed as a plating medium. Stools were plated on MacConkey agar to estimate the number of E. coli colonies and also plated on MacConkey-sorbitol agar to estimate the number of sorbitol-negative colonies of E. coli. These two approaches have proved useful for isolating and identifying E. coli O157:H7 form human feces and from feces of animals infected in the laboratory with this strain. The results suggest that media may be formulated in a similar fashion for detecting other specific strains of E. coli.

Agglutination Tests↗
PubMed2001

Evidence for a sorbitol transport system in immortalized human renal interstitial cells.

Sorbitol plays a major role in the maintenance of cell volume and functional integrity of several renal cells. Sorbitol synthesis takes place in inner collecting duct cells, whereas sorbitol dehydrogenase activity, which catalyzes the degradation of sorbitol to fructose, could mainly be detected in renal inner medullary interstitial cells. Therefore, we supposed that interstitial cells would require a sorbitol transport into the cells. However, such a transport system has not yet been described. Therefore, we have characterized the uptake of sorbitol in immortalized interstitial TK-173 cells, which were derived from human renal fibroblasts. Comparable to fresh isolated renal fibroblasts of the rat, immortalized TK-173 cells have a high sorbitol dehydrogenase activity. In this report, a temperature-dependent sorbitol uptake with saturation kinetics could be detected in immortalized TK-173 cells. The transport is characterized by a high velocity (Vmax 84 mmol/l x h) and an apparent Km of 10 mmol/l. The sorbitol uptake is independent of membrane potential, sodium, and chloride. Altogether, the physiological characteristics of this sorbitol transport are different from those of the osmotically regulated sorbitol efflux from epithelial cells. These results provide evidence that TK-173 cells derived from renal fibroblasts have a specific sorbitol transport. Furthermore, these data suggest a cooperation between epithelial and interstitial cells concerning osmoregulation.

Biological Transport↗
PubMed1993

Feeding sorbitol alone or in combination with monensin to finishing cattle.

Three trials were conducted with finishing steers to study the effect of feeding sorbitol alone or combined with monensin. For each trial 15 pens of eight steers were fed high-corn-silage diets. In the first two trials three pens of eight steers each were fed no additive, 35 g of sorbitol, 350 mg of monensin, or 30 g of sorbitol plus 350 mg of monensin per day. In Trial 1 three pens were fed 200 g of sorbitol per animal every 6 d, and in Trial 2 three pens were fed 60 g/d of sorbitol plus 350 mg/d of monensin. For the third trial, three pens were fed 0, 20, 40, or 80 g/d of sorbitol per animal and three pens were fed 40 g/d after 56 d; all the steers were fed 350 mg/d of monensin. In the first trial sorbitol had no effect on daily gain, and monensin increased (P < .05) daily gain. Intake of DM was lower (P < .05) for the steers fed sorbitol (35 g/d). Dry matter intake/gain was improved by feeding monensin (P < .05) or 35 g/d of sorbitol (P < .07). The improvement amounted to 18% when the additives were used in combination. In the second trial daily gains were similar for the cattle fed all diets. Dry matter intake was lower (P < .05) for steers fed monensin or 60 g/d of sorbitol and tended to be lower (P < .12) for the cattle fed 35 g/d of sorbitol. Dry matter intake/gain tended to be lower for cattle fed monensin and sorbitol, especially when fed in combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1998

Sorbitol as a test substance for measurement of liver plasma flow in humans.

The objective of this study was to evaluate whole-body removal kinetics of sorbitol, the use of extrarenal sorbitol clearance to estimate hepatic plasma flow in humans, and to compare measurements of liver flow by Fick's principle using either indocyanine green (ICG) or sorbitol. A sorbitol bolus (5 mmol/kg) was given intravenously to 6 controls for determination of sorbitol elimination capacity (SEC) and distribution volume, V(sorb)d. Sorbitol infusion (287 micromol/ min) was given to 17 liver patients and 11 controls. Extrarenal sorbitol clearance (V(sorb)x was calculated as infusion rate (corrected for renal excretion and accumulation in V(sorb)d) divided by arterial concentration. Liver flow (Q(ICG)) was calculated from the ICG infusion and arterial and hepatic venous ICG concentrations by Fick's principle. Average SEC was 73 micromol/min/kg, V(sorb)d was 0.16 L plasma per kilogram, and in vivo V(sorb)d was 3 mmol/L. Renal sorbitol excretion rate was 0.03 to 0.31 of infusion rate. Extrahepatic extrarenal removal was not significantly different from zero but varied considerably. Hepatic extraction fraction of sorbitol, (E(sorb)), measured by liver vein catheterization, was 0.35 to 1.04 (median, 0.86) in cirrhotic patients and 0.90 to 0.98 (0.86) in controls. The requirements for using Cl(sorb)x as an estimate of Q(ICG) was not violated by the data in controls, Cl(sorb)x/Q(ICG) 0.70 to 1.55 [median, 1.08]), whereas there was a systematic underestimation in cirrhotic patients (0.72-1.08 [0.85]). Liver flow calculated by Fick's principle using either sorbitol or ICG agreed well. E(sorb) > E(ICG) in each individual except one. Curvilinear relationship between E(sorb) and E(ICG) was in agreement with different kinetic parameters for sorbitol and ICG, and did not require additional assumption of intrahepatic shunts.

Adult↗
PubMedDate not supplied

Erythrocytic sorbitol contents in diabetic patients correlate with blood aldose reductase protein contents and plasma glucose levels, and are normalized by the potent aldose reductase inhibitor fidarestat (SNK-860).

The accumulation of sorbitol by the activated polyol pathway is considered to be a major cause of diabetic neuropathy. Because the erythrocytic sorbitol contents reportedly reflects that in nerves, erythrocytic sorbitol measurement would be useful for confirming the effect of an aldose reductase inhibitor (ARI). In this study, we examined erythrocytic sorbitol contents in healthy subjects and diabetic patients under fasting and postprandial conditions. Then, the contributions of blood aldose reductase (AR) contents and plasma glucose levels to the accumulated erythrocytic sorbitol contents were also analyzed. Erythrocytic sorbitol contents in the healthy subjects were 11.7 and 12.5-12.6 nmol/g Hb in fasting and postprandial status, respectively. In contrast, the erythrocytic sorbitol contents in diabetic patients were apparently higher (approximately 2.5-fold), but fidarestat treatment restored the elevated erythrocytic sorbitol contents to normal. In the diabetic patients, erythrocytic sorbitol contents were highly correlated with blood AR contents multiplied by the plasma glucose levels, whereas in the normal and fidarestat-treated diabetic patients no such correlation was observed. Taken together, these results suggest both the blood AR contents and the plasma glucose levels are factors determining erythrocytic sorbitol contents in diabetic patients. Notably, the potent ARI fidarestat was shown to normalize elevated erythrocytic sorbitol contents.

Aldehyde Reductase↗
PubMed1985

Intestinal absorption of sorbitol and effects of its acute administration on glucose homeostasis in normal rats.

Intestinal absorption of sorbitol was studied in a duodeno-jejunal loop of anaesthetized rats. The acute effects of exogenous sorbitol on glucose homeostasis were also evaluated in male and female rats. In the presence of lumen concentrations of sorbitol ranging from 1 microM to 200 mM, a fairly constant low percentage (about 12%) of the loop's contents was absorbed after 30 min. This amount increased only slightly with time, but this was not due to sorbitol accumulation in the mucosal layer of the loop. 3-O-methylglucose was absorbed much more quickly than sorbitol, but did not interfere with sorbitol absorption. The latter was not impaired by omission of lumen sodium ions nor by phloridzin, both of which inhibited 3-O-methylglucose absorption. Gastric administration of sorbitol did not affect plasma glucose or insulin levels. Glucose or sucrose administration caused a similar rise in plasma glucose, but the increase in plasma insulin levels was larger after glucose than after sucrose administration. Intravenous administration of sorbitol slightly increased plasma glucose and insulin levels. These changes were, however, considerably smaller than those occurring after glucose administration. In the normal rat, intestinal absorption of sorbitol is passive and proceeds at a low rate. Acute oral administration of sorbitol does not affect glucose homeostasis, which is only slightly disturbed by a large intravenous load of sorbitol.

3-O-Methylglucose↗
PubMed1988

Osmoregulation by slow changes in aldose reductase and rapid changes in sorbitol flux.

Renal medullary extracellular NaCl concentration is high during antidiuresis. To compensate, the cells accumulate large amounts of nonperturbing, osmotically active solutes (organic "osmolytes"), including sorbitol. GRB-PAP1 is a continuous line of epithelial cells from rabbit inner medulla. These cells accumulate sorbitol when medium NaCl concentration is elevated. The accumulation involves increase in aldose reductase, which catalyzes production of sorbitol from glucose. The purpose of the present study was to investigate control of cell sorbitol once aldose reductase was induced. We measured cell sorbitol, cell-to-medium sorbitol flux, and aldose reductase in cells grown in medium made hyperosmotic (600 mosmol/kg) with added NaCl and at intervals after medium osmolality was reduced to 300 mosmol/kg. In the hyperosmotic medium, cell sorbitol averaged 990 mmol/kg protein (approximately 260 mM), and its flux into the medium was 740 mmol.kg cell protein-1.day-1 (permeability less than 2 X 10(-9) cm/s). Within 5 min after return to isosmotic medium, sorbitol efflux increased greater than 150-fold. By the end of 1 day, cell sorbitol fell 77% but aldose reductase decreased only 10%. Aldose reductase then fell slowly to low levels over 2 wk. Thus renal medullary cells, chronically adapted to high NaCl, reduced their sorbitol level on return to isosmotic conditions by at least two mechanisms: 1) rapid increase in sorbitol flux into the medium, and 2) slow changes in the amount of aldose reductase.

Aldehyde Reductase↗
PubMed1994

Identification of a sorbitol permease in human erythrocytes.

Sorbitol, a polyol derived from glucose by the enzyme, aldose reductase, is a common organic solute in many cells. It plays a role in the osmotic regulation of epithelial cells and in the pathology of uncontrolled diabetes. To learn more about sorbitol transport, we measured D-[14C]sorbitol influx in human erythrocytes. Sorbitol influx at 37 degrees C was a linear function of sorbitol concentration over the range of 0.05-100 mM. The activation energy for sorbitol influx was 10.0 kcal/mol, and the Q10 over the range 10-50 degrees C was 1.8, higher than predicted for diffusion through an aqueous pore. Glucose transport inhibitors either had no effect (1 mM phloridzin) or minimally inhibited (approximately 35% inhibition by 10 microM cytochalasin B or 250 microM phloretin) sorbitol influx. Influx was stimulated twofold by 0.5 mM p-chloromercuribenzoic acid, an inhibitor of glucose transport, and this was reversed by 2 mM dithiothreitol. Sorbitol influx was neither Na dependent nor sensitive to changes in cell volume. Glucose, fructose, mannitol, myo-inositol, and gluconate, at four- to fivefold molar excesses over sorbitol, did not inhibit its influx. We conclude that there is a specific sorbitol transport pathway in human erythrocytes similar to the sorbitol permease in renal epithelial cells.

Animals↗
PubMed1994

Further characterization of the sorbitol permease in PAP-HT25 cells.

The sorbitol permease enables the efflux of sorbitol from cultured rabbit papillary cells (PAP-HT25) in response to a reduction in osmolality. The anion transport inhibitor 5-nitro-2-(3-phenylpropylamino)benzoate (100 microM) inhibited efflux by 92%, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.5 mM) reduced efflux by 40%. 2,4-Dinitrobenzenesulfonate and p-chloromercuriphenylsulfonic acid had no effect. The protease trypsin (0.05 mg/ml) reduced sorbitol efflux by 53%, pronase (0.01 mg/ml) by 47%, and papain (0.1 mg/ml) by 49%; chymotrypsin had no effect. Sugars and sugar alcohols at different concentrations (10-200 mM) in the bathing solution did not influence sorbitol efflux. Determination of the osmotically induced influx of sugar alcohols showed that xylitol uptake was faster than that of sorbitol; 6-deoxysorbitol was slower; L-sorbitol, arabitol, galactitol, and 2-deoxysorbitol entered at the same rate as sorbitol; and maltitol did not enter the cells. Sorbitol and 6-deoxysorbitol at 9 mM competitively inhibited [14C]sorbitol influx by 24 and 32%, respectively, whereas xylitol, taurine, betaine, and myo-inositol showed no inhibition. We conclude that 1) a specific inhibitor of the permease was not found, 2) the sorbitol permease or associated regulator is a protein, and 3) the C-6 atom of sorbitol is important in the selectivity of the permease.

Animals↗
PubMed1996

Osmotic regulation of sorbitol in the thick ascending limb of Henle's loop.

Organic osmolytes, such as sorbitol, inositol, glycerophosphorylcholine, and betaine, play an important role in the osmoregulation of inner medullary cells of the kidney. The cells of the outer medulla are also exposed to elevated NaCl and urea concentrations during antidiuresis. Therefore, we investigated the mechanisms involved in the regulation of outer medullary organic osmolytes, especially cell sorbitol content of immortalized epithelial cells of the thick ascending limb of Henle's loop (TALH). In the cultured cell model, a 600 mosmol/l medium (osmolarity adjusted by addition of 150 mM NaCl or 300 mM sucrose) increased the intracellular sorbitol content significantly compared with a 300 mosmol/l medium. The accumulation of sorbitol appeared to be due to an increase of aldose reductase activity, which catalyzed sorbitol synthesis. Sorbitol degradation by sorbitol dehydrogenase was not detectable under our experimental conditions. After a sudden decrease of the extracellular osmolarity, the sorbitol permeability of the cellular membrane increased sevenfold within 10 min compared with isosmolar conditions. These results indicate that sorbitol, like inositol, plays an important role in the osmoregulation of TALH cells. Although the short-term regulation involves rapid changes in sorbitol membrane permeability, the longterm adaptation to low osmolarities is regulated by intracellular sorbitol synthesis.

Aldehyde Reductase↗
PubMed1991

Crucial role of aldose reductase activity and plasma glucose level in sorbitol accumulation in erythrocytes from diabetic patients.

Increased sorbitol levels have been demonstrated in tissues of diabetic patients. Although tissue sorbitol levels correlate with plasma glucose levels, a large variability in sorbitol levels has been observed among diabetic patients with similar plasma glucose levels. This variability in tissue sorbitol levels may be due to differences in the activity of aldose reductase, the enzyme that converts glucose to sorbitol. In this study, we isolated aldose reductase from erythrocytes of 31 diabetic patients and 6 nondiabetic control subjects, measured its activity, and compared it to simultaneously measured erythrocyte sorbitol levels. The activity of erythrocyte aldose reductase was increased in diabetic patients compared with control subjects (28.1 +/- 1.4 vs. 22.4 +/- 1.7 nmol.min-1.g-1 Hb, P less than 0.05), but there was an approximately threefold variation in aldose reductase activity among diabetic patients. Erythrocyte aldose reductase activity and fasting plasma glucose levels significantly correlated with the erythrocyte sorbitol level in all individuals (r = 0.48, P less than 0.005 and r = 0.63, P less than 0.005, respectively). The sorbitol level was higher in patients with high aldose reductase activity than in those who had low enzyme activity for any given level of glycemia. The sorbitol production rate calculated from Km and Vmax values showed a better correlation with the erythrocyte sorbitol level (r = 0.80, P less than 0.005), and there was also a good correlation between the erythrocyte sorbitol level and the product of aldose reductase activity by plasma glucose level (r = 0.70, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Experience with hypotonic 2.5% sorbitol solution as an irrigating fluid in transurethral resection of the prostate.

19 patients were studied in connection with transurethral resection of the prostate using the intermittent technique and hypotonic 2.5% sorbitol solution as an irrigating fluid. No diuretics were given postoperatively. In 2 patients there was a slight elevation of the serum creatinine level preoperatively but in 17 patients serum creatinine was within the reference limits. The plasma sorbitol concentration was determined at 20-min intervals for two hours. The mean plasma concentration of sorbitol immediately postoperatively was 379 mg/l (2.1 mmol/l) and the highest level observed was 1,900 mg/l (10.6 mmol/l). The half-life for sorbitol in plasma was 21 min (mean calculated in 11 cases). The range was 11-33 min. With increasing immediate postoperative plasma sorbitol levels there was also an increase in the half-life, corresponding to saturation of the sorbitol metabolizing enzyme system. The absorbed fluid volumes were calculated from the immediate postoperative plasma concentration of sorbitol, which gave a mean of 0.23 1 and a maximum of 1.01. Haemodilution effects with decrease in the serum sodium and serum albumin concentrations were noted, but they were much less marked than when 5% sorbitol solution was used as an irrigating fluid. There were only insignificant increases in the plasma haemoglobin concentrations postoperatively, which were probably due to heat decomposition of red blood cells in the bladder during the operation. About 7% of the absorbed amount of sorbitol was eliminated in the urine (mean). The highest value observed was 18% in the case showing the highest plasma sorbitol concentration immediately postoperatively (1,900 mg/l). Sorbitol was eliminated in the urine over a period of 6 hours postoperatively.

Aged↗
PubMed1989

[Glucose stimulates the absorption of sorbitol through the human jejunal mucosa].

Digestive tolerance of sorbitol in man varies according to whether it is taken in an empty stomach or during the meal. This suggests a regulatory step in the absorption of sorbitol in the small intestine. The mechanism of intestinal transport of sorbitol was studied in vitro in jejunal fragments obtained by endoscopy or by surgery. The intracellular concentration (C) of sorbitol was measured at stationary state in the presence of 10 mmol sorbitol in the incubation medium (M). The ratio C/M was less than 1 (0.66 +/- 0.04, mean +/- SEM) and was not modified by phloridzin (0.63 +/- 0.06) or metabolic inhibitors (0.59 +/- 0.03) but was diminished by ouabain (0.5 +/- 0.05, p less than 0.05). The influx of sorbitol across the luminal membrane increased linearly with increasing concentration of sorbitol in the medium and was more pronounced in the presence of glucose (p less than 0.01). Unlike glucose, addition of sorbitol to the mucosal side did not enhance the absorption of sodium as monitored by the increase in short circuit current in Ussing chambers. A net absorption of sorbitol stimulated by glucose was observed. The absorption of sorbitol can be explained by a simple diffusional component dependent on the concentration gradient of sorbitol and by another yet unidentified mechanism stimulated by glucose.

Biological Transport↗
PubMed1997

Mechanism of the stabilization of ribonuclease A by sorbitol: preferential hydration is greater for the denatured then for the native protein.

The effect of interactions of sorbitol with ribonuclease A (RNase A) and the resulting stabilization of structure was examined in parallel thermal unfolding and preferential binding studies with the application of multicomponent thermodynamic theory. The protein was stabilized by sorbitol both at pH 2.0 and pH 5.5 as the transition temperature, Tm, was increased. The enthalpy of the thermal denaturation had a small dependence on sorbitol concentration, which was reflected in the values of the standard free energy change of denaturation, delta delta G(o) = delta G(o) (sorbitol) - delta G(o)(water). Measurements of preferential interactions at 48 degrees C at pH 5.5, where protein is native, and pH 2.0 where it is denatured, showed that sorbitol is preferentially excluded from the denatured protein up to 40%, but becomes preferentially bound to native protein above 20% sorbitol. The chemical potential change on transferring the denatured RNase A from water to sorbitol solution is larger than that for the native protein, delta mu(2D) > delta mu(2N), which is consistent with the effect of sorbitol on the free energy change of denaturation. The conformity of these results to the thermodynamic expression of the effect of a co-solvent on denaturation, delta G(o)(W) + delta mu(D)(2)delta G(o)(S) + delta mu(2D), indicates that the stabilization of the protein by sorbitol can be fully accounted for by weak thermodynamic interactions at the protein surface that involve water reversible co-solvent exchange at thermodynamically non-neutral sites. The protein structure stabilizing action of sorbitol is driven by stronger exclusion from the unfolded protein than from the native structure.

Enzyme Stability↗
PubMed1989

Intracellular sorbitol content in isolated rat inner medullary collecting duct cells. Regulation by extracellular osmolarity.

In order to study the mechanisms involved in the regulation of renal inner medullary sorbitol content, collecting duct cells were isolated from rat inner medulla and the effect of extracellular osmolarity on sorbitol synthesis and sorbitol content was investigated. Cells isolated at 300 mosmol/l and incubated up to 24 h as primary cultures in 300 mosmol/l media or in media made 600 mosmol/l by the addition of 150 mM NaCl showed no difference in total synthesis. Intracellular sorbitol content was, however, 2.3-fold higher in the cells kept in the higher osmotic medium. Cells isolated at 600 mosmol/l released sorbitol about 8 times faster when transferred into hypoosmotic medium (300 mosmol/l) than when transferred into isoosmotic (600 mosmol/l) media. Cells exposed to hyperosmotic media (900 mosmol/l with NaCl) maintained a higher intracellular sorbitol content than cells incubated in isoosmotic media. Changes of intracellular sorbitol content could not be attributed entirely to cell lysis--as demonstrated by determination of cellular content of lactate and lactate dehydrogenase. The alteration in sorbitol membrane permeability was reversible and was only observed when poorly permeable solutes (such as NaCl and sucrose) were used for the experiments, changes in urea elicited no effect. It is proposed that rapid changes in membrane permeability to sorbitol play an important role in the adjustment of intracellular sorbitol concentration in inner medullary collecting duct cells to changes in extracellular osmolarity.

Animals↗
PubMed1990

Cost-effective treatment of constipation in the elderly: a randomized double-blind comparison of sorbitol and lactulose.

PURPOSE: The purpose of this study was to evaluate the use of sorbitol as an inexpensive alternative to lactulose for treating constipation in the elderly. PATIENTS AND METHODS: Thirty men aged 65 to 86 with chronic constipation were studied in a randomized, double-blind, cross-over trial in which lactulose and 70% sorbitol (0 to 60 mL daily) were each given for 4 weeks preceded by a 2-week washout period. RESULTS: The average number of bowel movements per week was 6.71 with sorbitol and 7.02 with lactulose (95% confidence interval of the difference: -0.43 to 1.06), and the average number of days per week with bowel movements was 5.23 with sorbitol and 5.31 with lactulose (95% confidence interval of the difference: -0.32 to 0.48). Eleven patients stated a preference for sorbitol, 12 for lactulose, and seven had no preference. On a visual analogue scale measuring severity of constipation (0 to 100 mm), the average score for sorbitol was 35.6 mm versus 37.1 mm for lactulose (95% confidence interval of the difference: -6.4 to 9.3). The sorbitol and lactulose treatment periods were also similar in percent of bowel movements recorded as "normal," frequency and severity of symptoms such as bloating, cramping, and excessive flatulence, and overall health status as assessed by a previously validated five-category questionnaire. There were no significant differences between sorbitol and lactulose in any outcome measured except nausea, which was increased with lactulose (p less than 0.05). CONCLUSION: These results support the hypothesis that sorbitol and lactulose have no clinically significant differences in laxative effect. Sorbitol can be recommended as a cost-effective alternative to lactulose for the treatment of constipation in the elderly.

Aged↗
PubMed1983

The effects of an aldose reductase inhibitor upon the sorbitol pathway, fructose-1-phosphate and lactate in the retina and nerve of streptozotocin-diabetic rats.

UNLABELLED: To investigate the aetiology of complications secondary to experimental diabetes in the rat, the concentrations of glucose, sorbitol, fructose, fructose-1-phosphate, lactate and inositol were measured in the retina and sciatic nerve of streptozotocin-diabetic and normal rats treated for 22 days with ICI 105552 (1-(3,4-dichlorobenzyl)-3-methyl-1,2-dihydro-2-oxoquinol-4-ylacetic acid, sodium salt; 50 mg/kg body wt daily), an inhibitor of aldose reductase (E.C. 1.1.1.21) the first enzyme of the sorbitol pathway. In the diabetic nerve, where accumulation of sorbitol may be pathogenic, treatment with ICI 105552 reduced the accumulations of sorbitol (70%), fructose (47%) and lactate (34%) without affecting glucose, fructose-1-phosphate or inositol. In the nerves of controls, the inhibitor reduced both sorbitol (23%) and fructose (20%) levels without other effects. In the diabetic retina where accumulation of sorbitol or lactate might be pathogenic, treatment with ICI 105552 had no statistically significant effect upon the concentrations of glucose, sorbitol, fructose, fructose-1-phosphate or inositol. However, the inhibitor reduced the concentration of lactate to below the non-diabetic level. In the retinas of controls, dosage with ICI 105552 reduced the concentration of sorbitol by 36% without other effects. THE RESULTS: (1) demonstrated that ICI 105552 was a potent inhibitor of aldose reductase in sciatic nerve and suggested that a proportion of nerve lactate in diabetes could result from sorbitol pathway activity; (2) implied that flux through the sorbitol pathway, eventually to form lactate, increases in diabetic retina; and (3) indicated, by the drug's reduction of retinal lactate concentration, that inhibitors of aldose reductase might be of potential use in diabetic retinopathy.

Aldehyde Reductase↗