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PubMed1985

Red cell sorbitol and diabetic control.

There is a disagreement about the value of red cell sorbitol as an indicator of diabetic control. We studied 7 insulin requiring diabetics, one for 10 days and 6 for 24 hours. In the 10-day study, blood samples were obtained every 4-6 hours. Sequential analysis of plasma glucose and red cell sorbitol levels showed that simultaneous levels had the best correlation r = 0.534, P less than .001. In the 24-hour studies, blood samples were obtained at 1 to 4-hour intervals. Three of the 6 patients showed the best correlation between simultaneous plasma glucose and red cell sorbitol, with r = 0.727 to 0.957 and P less than .001 to P less than .07. When plasma glucose values were compared to red cell sorbitol levels 1, 2, 4, 8 and 12 h later, correlation coefficients were not as good as the simultaneous comparison. We conclude that the measurement of red cell sorbitol correlates well with simultaneous plasma glucose in some but not all diabetic subjects and provides no additional information to the clinician.

Adult↗
PubMed2003

Aldose reductase induced by hyperosmotic stress mediates cardiomyocyte apoptosis: differential effects of sorbitol and mannitol.

Cells adapt to hyperosmotic conditions by several mechanisms, including accumulation of sorbitol via induction of the polyol pathway. Failure to adapt to osmotic stress can result in apoptotic cell death. In the present study, we assessed the role of aldose reductase, the key enzyme of the polyol pathway, in cardiac myocyte apoptosis. Hyperosmotic stress, elicited by exposure of cultured rat cardiac myocytes to the nonpermeant solutes sorbitol and mannitol, caused identical cell shrinkage and adaptive hexose uptake stimulation. In contrast, only sorbitol induced the polyol pathway and triggered stress pathways as well as apoptosis-related signaling events. Sorbitol resulted in activation of the extracellular signal-regulated kinase (ERK), p54 c-Jun N-terminal kinase (JNK), and protein kinase B. Furthermore, sorbitol treatment resulting in induction and activation of aldose reductase, decreased expression of the antiapoptotic protein Bcl-xL, increased DNA fragmentation, and glutathione depletion. Apoptosis was attenuated by aldose reductase inhibition with zopolrestat and also by glutathione replenishment with N-acetylcysteine. In conclusion, our data show that hypertonic shrinkage of cardiac myocytes alone is not sufficient to induce cardiac myocyte apoptosis. Hyperosmolarity-induced cell death is sensitive to the nature of the osmolyte and requires induction of aldose reductase as well as a decrease in intracellular glutathione levels.

Aldehyde Reductase↗
PubMed1992

Sorbitol in isolation of rat pancreatic islets. Effects on islet yield, insulin secretion and accumulation of inositol phosphates.

Tissue aggregation and exocrine contamination are problems encountered in gradient separation of pancreatic islets. Here we report that sorbitol used as an osmotic component in Percoll gradients gives a low ionic strength gradient with improved purity of islet fraction, less islet aggregation and reduced time for final manual rinsing following separation in gradients with NaCl as osmotic component. Previous reports have indicated that long-term (weeks) exposure to high sorbitol concentrations leads to low intracellular levels of inositol phosphates and subsequent effects on the intracellular signal transduction in cells. In our model, short-term exposure to high sorbitol concentrations had no effect on the accumulation of the inositol phosphates or insulin secretion caused by glucose. On the other hand, sorbitol increased the basal insulin secretion three-fold, apparently via a non-stimulatory mechanism. Therefore, we conclude that sorbitol is preferable to NaCl as the osmotic component in Percoll gradient separation of rat pancreatic islets, although long-term exposure should be avoided due to potential toxic effects.

Animals↗
PubMed2003

Effectiveness of the sorbitol H2 breath test in detecting histological damage among relatives of coeliacs.

BACKGROUND: Small intestinal lesions have a wide severity in coeliac disease (CD), and early diagnosis is important in preventing neoplastic and non-neoplastic disorders related to CD. The aim of this study was to compare the effectiveness of the sorbitol H2 breath test (H2-BT) and serological tests (antigliadin (AGA), antiendomysium (EMA) and anti-tissue transglutaminase (anti-tTG)) as screening tests in the detection and estimation of CD prevalence in 1st-degree relatives. METHODS: Screening was performed in 111 1st-degree relatives of 37 coeliac families. Sorbitol H2-BT, AGA, EMA and anti-tTG antibodies were used to select the candidates for small-bowel biopsy. Relatives with abnormal serological tests and/or with sorbitol H2-BT positivity underwent a small-bowel biopsy. Small-bowel biopsy was also performed in relatives negative in all tests but with clinical complaints or suspected of having CD, and intestinal lesions were expressed according to the Marsh classification. RESULTS: CD was diagnosed in 49/111 screened relatives (44.14%): 5 showed Marsh IIIc, 8 Marsh IIIb, 16 Marsh IIIa, 13 Marsh II and 7 Marsh I lesions. Nineteen relatives showed the classical form of the disease, while the subclinical and silent forms were recorded in 20 and 10, respectively. AGA, EMA and anti-tTG showed strong positivity only in severe intestinal damage (Marsh IIIb-c lesions) (but overall positivity was 36.73%, 38.78% and 44.89% for AGA, EMA and anti-tTG, respectively), while sorbitol H2-BT showed strong positivity also in patients with slight histological damage (Marsh I-IIIa) (overall positivity was 83.67%). CONCLUSIONS: A significant proportion of coeliacs may be missed if relatives are screened by serology only, while the efficacy of sorbitol H2-BT in screening relatives is confirmed. This study confirms that neither a breath test nor serology can replace intestinal biopsy, which remains the gold standard for the diagnosis of CD.

Adolescent↗
PubMed1988

Absence of lactate accumulation on transurethral resection of the prostate using 2.5% sorbitol solution as an irrigating fluid.

19 patients with benign hyperplasia of the prostate were studied. During transurethral resection of the prostate, 2.5% sorbitol solution was used as an irrigating fluid. Blood samples were taken preoperatively, immediately postoperatively, and 60 and 120 min postoperatively. Samples were analysed for sorbitol metabolites (fructose, glucose, lactate and pyruvate) and inorganic phosphate. The series was divided into two groups, one with low absorption and one with high absorption of irrigating fluid. The limit for the plasma sorbitol concentration immediately postoperatively, dividing the groups, was 1.0 mmol/l, corresponding to an absorbed fluid volume of about 0.1 l. There was a slight increase in lactate and a significant decrease in pyruvate in the blood in both groups postoperatively. Blood fructose was zero in the group with low absorption of irrigating fluid whereas there was a slight increase in the group with high absorption, with a maximum of 0.53 mmol fructose/l. Blood glucose did not show any significant changes postoperatively. Inorganic phosphate in serum showed a significant decrease postoperatively in both groups. There were no significant differences between the groups at the various postoperative sampling times with regard to lactate, pyruvate, glucose or inorganic phosphate in the blood. Thus, we did not observe any accumulation of lactate in the blood when using 2.5% sorbitol solution as an irrigating fluid with absorbed fluid volumes up to 1 litre (corresponding to 25 g sorbitol).

Blood Glucose↗
PubMedDate not supplied

Increased sorbitol pathway activity generates oxidative stress in tissue sites for diabetic complications.

Chronic diabetic complications, in particular, nephropathy, peripheral and autonomic neuropathy, "diabetic foot," retinopathy, and cardiovascular disease, remain the major cause of morbidity and mortality in patients with diabetes mellitus. Growing evidence indicates that both increased activity of the sorbitol pathway of glucose metabolism and enhanced oxidative stress are the leading factors in the pathogenesis of diabetic complications. The relation between the two mechanisms remains the area of controversy. One group has reported that increased sorbitol pathway activity has a protective rather than detrimental role in complication-prone tissues because the pathway detoxifies toxic lipid peroxidation products. Others put forward a so-called "unifying hypothesis" suggesting that activation of several major pathways implicated in diabetic complications (e.g., sorbitol pathway) occurs due to increased production of superoxide anion radicals in mitochondria and resulting poly(ADP-ribose) polymerase activation. This review (a) presents findings supporting a key role for the sorbitol pathway in oxidative stress and oxidative stress-initiated downstream mechanisms of diabetic complications, and (b) summarizes experimental evidence against a detoxifying role of the sorbitol pathway, as well as the "unifying concept."

Aldehyde Reductase↗
PubMed2004

Sorbitol uptake is regulated by glucose through the hexokinase pathway in vegetative peach-tree buds.

In peach trees (Prunus persica L. Batsch cv. Redhaven), sorbitol is a primary photosynthetic product and may play an important role in the budbreak process. Surprisingly, before budbreak (from January to early March), the concentration of sorbitol in the xylem sap decreases, while that of hexoses (glucose and fructose) increases. The aim of this work was to study the control of sorbitol uptake into vegetative buds by hexoses. Sorbitol uptake was selectively inhibited by hexoses at low and physiological concentrations and this effect was both reversible and concentration-dependent. In addition, the active uptake of sorbitol significantly declined in the plasma membrane vesicles-enriched fraction purified from glucose-treated vegetative buds, suggesting that the inhibitory action of glucose was at the membrane level. Finally, among several glucose analogues tested, only hexokinase substrates (2-deoxyglucose and mannose) were able to mimic the glucose effect, which was completely blocked by the hexokinase inhibitor mannoheptulose. These results represent the first steps towards a better understanding of polyol transport control in plants.

Biological Transport↗
PubMed2001

Upper gastrointestinal tract injury in patients receiving kayexalate (sodium polystyrene sulfonate) in sorbitol: clinical, endoscopic, and histopathologic findings.

Kayexalate (sodium polystyrene sulfonate) in sorbitol has been demonstrated to cause colonic necrosis in a subset of uremic patients who are administered the cation exchange resin for treatment of hyperkalemia. Upper gastrointestinal damage associated with Kayexalate in sorbitol is reported far less frequently, and the clinicopathologic spectrum of disease in cases with upper gastrointestinal damage has not been investigated previously. The authors studied the clinical, endoscopic, and histologic features of 11 patients with Kayexalate crystals in biopsies from the esophagus (n = 7), stomach (n = 6), and duodenum (n = 2). The endoscopic appearance was markedly abnormal in all 11 patients. The effects of the medication closely mimicked other endoscopic and radiologic diagnoses in three cases, including esophageal carcinoma, Candidal esophagitis, and gastric bezoar. Histologic and/or endoscopic evidence of mucosal injury in the form of an ulcer or erosion was present in nine patients (82%). In four patients with mucosal injury, no other etiology apart from Kayexalate in sorbitol could be identified. In comparison with a cohort of patients with Kayexalate crystals in lower gastrointestinal specimens identified during the same period (11 patients) the frequency of associated mucosal damage was not significantly different (55%, p = 0.19), but no patient with upper gastrointestinal Kayexalate required surgical resection or died as a result of Kayexalate-induced mucosal injury. The results of this study provide evidence that Kayexalate in sorbitol can induce damage to the upper gastrointestinal tract. Recognition of Kayexalate crystals in histologic sections as a marker for sorbitol-induced mucosal damage may aid in establishing the correct diagnosis for clinically or endoscopically misleading lesions.

Aged↗
PubMed1987

Effect of charcoal and sorbitol-charcoal suspension on the elimination of intravenous phenobarbital.

The effects of two different oral charcoal suspensions on the elimination of a 200 mg/70 kg, 1 h intravenous (i.v.) infusion of phenobarbital and the tolerances of the two regimens were determined in a randomized crossover study in six healthy male volunteers. Phenobarbital was given i.v. alone or together with 105 g of oral activated charcoal suspension or with 105 g of a commercially available sorbitol-charcoal suspension over a 36-h period. A 13-34% decrease in the area under the serum concentration time curve (AUC) for 0-60 h occurred with the administration of the activated charcoal, and a 19-52% decrease occurred with the commercial sorbitol-charcoal regimen. The mean apparent systemic clearance of total phenobarbital increased from 0.089 +/- 0.019 ml/min/kg to 0.141 +/- 0.029 and 0.146 +/- 0.036 ml/min/kg with the charcoal and sorbitol-charcoal treatments, respectively. No significant change in the fraction of phenobarbital bound to protein was detected. The charcoal regimen caused constipation in one subject. All subjects taking the sorbitol-charcoal preparation experienced diarrhea; there were no changes in electrolytes with either charcoal suspension. All subjects preferred the sorbitol-charcoal preparation.

Adult↗
PubMed1980

Sucrose and sorbitol as sweeteners in the diet of insulin-dependent diabetics.

Blood glucose levels following breakfast meals containing sorbitol or sucrose as sweeteners were investigated. Nine insulin-treated diabetics received two test meals after an overnight fast. The meals were composed of 90 g white bread, 9 g butter and 100 g strawberry jam which on one occasion contained 18 g sorbitol as sweetener and on another 18 g sucrose. Blood glucose was measured for three hours following the meal. The test meal sweetened with sucrose showed a slightly faster postprandial rise in blood glucose than the sorbitol-sweetened meal, but this difference is not statistically significant at any point of the curves. Taking into consideration that sorbitol has a sweetening effect of only 60% of that of sucrose, we conclude that neither sucrose nor sorbitol are acceptable sweeteners for insulin-dependent diabetics.

Adolescent↗
PubMed2005

Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth and sugar malabsorption (lactose, fructose, sorbitol) may play a role in irritable bowel syndrome. The lactulose breath test is a reliable and non-invasive test for the diagnosis of small intestinal bacterial overgrowth. The lactose, fructose and sorbitol hydrogen breath tests are widely used to detect specific sugar malabsorption. AIM: To assess the extent to which small intestinal bacterial overgrowth may influence the results of hydrogen sugar breath tests in irritable bowel syndrome patients. METHODS: We enrolled 98 consecutive irritable bowel syndrome patients. All subjects underwent hydrogen lactulose, lactose, fructose and sorbitol hydrogen breath tests. Small intestinal bacterial overgrowth patients were treated with 1-week course of antibiotics. All tests were repeated 1 month after the end of therapy. RESULTS: A positive lactulose breath test was found in 64 of 98 (65%) subjects; these small intestinal bacterial overgrowth patients showed a significantly higher prevalence of positivity to the lactose breath test (P < 0.05), fructose breath test (P < 0.01) and sorbitol breath test (P < 0.01) when compared with the small intestinal bacterial overgrowth-negatives. Small intestinal bacterial overgrowth eradication, as confirmed by negative lactulose breath test, caused a significant reduction in lactose, fructose and sorbitol breath tests positivity (17% vs. 100%, 3% vs. 62%, and 10% vs. 71% respectively: P < 0.0001). CONCLUSIONS: In irritable bowel syndrome patients with small intestinal bacterial overgrowth, sugar breath tests may be falsely abnormal. Eradication of small intestinal bacterial overgrowth normalizes sugar breath tests in the majority of patients. Testing for small intestinal bacterial overgrowth should be performed before other sugar breath tests tests to avoid sugar malabsorption misdiagnosis.

Adult↗
PubMed2006

An engineered sorbitol cycle alters sugar composition, not growth, in transformed tobacco.

Many efforts have been made to engineer stress tolerance by accumulating polyols. Transformants that accumulate polyols often show growth inhibition, because polyols are synthesized as a dead-end product in plants that do not naturally accumulate polyols. Here, we show a novel strategy in which a sorbitol cycle was engineered by introducing apple cDNA encoding NAD-dependent sorbitol dehydrogenase (SDH) in addition to sorbitol-6-phosphate dehydrogenase (S6PDH). Tobacco plants transformed only with S6PDH showed growth inhibition, and very few transformants were obtained. In contrast, many transgenic plants with both S6PDH and SDH were easily obtained, and their growth was normal despite their accumulation of sorbitol. Interestingly, the engineered sorbitol cycle enhanced the accumulation of sucrose instead of fructose that was expected to be increased. Sucrose, rather than fructose, was also increased in the immature fruit of tomato plants transformed with an antisense fructokinase gene in which the phosphorylation of fructose was inhibited. A common phenomenon was observed in the metabolic engineering of two different pathways, showing the presence of homeostatic regulation of fructose levels.

Antisense Elements (Genetics)↗
PubMed1995

Thermal stability of human immunoglobulins with sorbitol. A critical evaluation.

The effect of the additive sorbitol on the thermal stabilization of human IgG was investigated by differential scanning calorimetry and size exclusion chromatography. In the presence of 33% sorbitol, the temperature at which denaturation of IgG began (Ti) was increased from 52 to 65 degrees C. Similarly, the temperature of the maximum heat capacity (Tmax) was increased from 69 to 76 degrees C. Sorbitol also decreased dimer aggregation and the extent of oligomerization during heating compared with IgG dissolved in phosphate buffer. Sorbitol at 33% prevented massive protein denaturation but a 10-15% of oligomerization of high molecular weight aggregates with turbidity could not be avoided when heating for 10 h at 60 degrees C. The use of sorbitol 33% to avoid heat denaturation of human IgG during viral inactivation did not prevent protein aggregation or the appearance of turbidity. Consequently, further processing will be required to achieve a product suitable for pharmaceutical use.

Calorimetry, Differential Scanning↗
PubMed1981

Effect of aqueous solutions of sorbitol-xylitol on plaque metabolism and on growth of Streptococcus mutans.

The present study showed that the growth of Streptococcus mutans strain GS5 was inhibited by xylitol, and this indicates together with previous reports that this is a common phenomenon in this species. Sorbitol was found to increase the growth of S. mutans strains OMZ 176 and GS5 slightly compared with cultures with no external carbon source. Addition of small amounts of xylitol to the sorbitol cultures gave a growth below that of cultures with no extra carbon. Dental plaque challenged with sorbitol gave a small pH drop whereas xylitol caused a negligible decrease in pH. Sorbitol-xylitol challenges gave less acid production than sorbitol challenges alone.

Adult↗
PubMed1995

Effect of xylitol-containing chewing gum on sorbitol metabolism in dental plaque.

The aim of the present study was to examine whether a long-term use of chewing gum with xylitol as the only sweetener would affect sorbitol metabolism in dental plaque. Ten test subjects used xylitol-sweetened chewing gum for 12 weeks. Plaque was collected at three occasions; 1) Control plaque; 2) Test plaque I: plaque collected after 12 weeks of chewing xylitol-containing chewing gum; 3) Test plaque II: sucrose-stimulated plaque collected 2 d after Test plaque I was collected. Plaque suspensions were incubated with [14C]sorbitol, and uptake of sorbitol and production of sorbitol metabolites were determined by HPLC. Plaque formation and sorbitol uptake were significantly reduced.

Adaptation, Physiological↗
PubMed1991

Influence of glucose, fructose and aldose reductase inhibition on retinal sorbitol metabolism.

The sorbitol shunt has been studied in bovine retinal tissue at incubation times from 1 to 24 h. It was shown that an elevated glucose concentration (22 mM) of the medium was accompanied by a slight increase in sorbitol content already after 3 h. At longer incubation times, but lower glucose concentration (11.1 mM) there was a similar increase. Addition of an aldose reductase (AR) inhibitor prevented the sorbitol increase. Addition of fructose to the medium significantly increased the sorbitol accumulation above the effect seen with glucose alone and this effect was not influenced by the AR inhibitor. Thus the sorbitol concentration in the retina may be increased after a short incubation time and further enhanced by the presence of fructose.

Aldehyde Reductase↗
PubMed1983

Effect of sucrose phosphate and sorbitol on infectivity of enveloped viruses during storage.

Cytomegalovirus and varicella-zoster virus recovery from sucrose phosphate (0.2 M SP) and 70% sorbitol (sorbitol) was compared after storage at -70, 4, and 20 degrees C over time. Recovery from 0.2 M SP was uniformly better. More tissue culture infective doses and infectious foci were recovered in cell monolayers inoculated with 0.2 M SP virus stocks as compared with viruses stored in 70% sorbitol. Although both viruses were isolated from diluted fresh stocks (10(-1) through 10(-4], freezing diluted virus suspensions generally resulted in diminished recovery. Similar stabilizing effects on respiratory syncytial virus and herpes simplex virus type 1 infectivities were observed when stocks were preserved in 0.2 M SP, as compared with 70% sorbitol. Overall, 0.2 M SP was better than 70% sorbitol for stabilizing cytomegalovirus, varicella-zoster virus, respiratory syncytial virus, and herpes simplex virus type 1 infectivities under the conditions tested.

Cytomegalovirus↗
PubMed1991

Intracellular betaine substitutes for sorbitol in protecting renal medullary cells from hypertonicity.

Renal medullary cells are normally exposed to a variably high extracellular NaCl concentration. They compensate by accumulating large amounts of organic osmolytes, including sorbitol and betaine. The sorbitol is synthesized from glucose, catalyzed by aldose reductase. Previously, inhibition of aldose reductase activity was noted to greatly reduce renal medullary cell survival and growth (measured by cloning efficiency) in tissue cultures of renal medullary cells in hypertonic medium. In contrast, inhibition of aldose reductase and renal medullary sorbitol accumulation is not associated with kidney damage in vivo. In the present experiments we find that addition of betaine to the medium, and its resultant uptake by the cells, largely replaces the decrease in sorbitol caused by aldose reductase inhibitors and restores the cloning efficiency. We presume that in vivo uptake of betaine by renal medullary cells similarly protects them from harm when aldose reductase inhibitors lower sorbitol. The results also demonstrate that one organic osmolyte can substitute for another in protecting cells from hypertonicity, consistent with the compatible osmolytes hypothesis.

Aldehyde Reductase↗