Erythrocyte Sorbitol Research Articles

Effect of oral glucose loading on erythrocyte sorbitol in diabetic and non-diabetic subjects

Effect of oral glucose loading on erythrocyte sorbitol in diabetic and non-diabetic subjects

P-6-20 Erythrocyte sorbitol levels fluctuate rapidly in response to changes in ambient glucose concentration

P-6-20 Erythrocyte sorbitol levels fluctuate rapidly in response to changes in ambient glucose concentration

Effects of hyperglycaemia and sorbitol accumulation on erythrocyte deformability in diabetes mellitus.

Erythrocyte deformability was studied in a total of 83 poorly controlled diabetics (mean blood glucose 12.2 mmol/l) who were divided into three groups, each with matched healthy controls. There was no appreciable difference between diabetics and matched controls regarding the filtration of erythrocytes through 3 micron diameter straight channel pores (25 diabetics) or tortuous channel pores (28 diabetics), or for the measurement of erythrocyte elongation over a range of osmolalities in the Ektacytometer (30 diabetics). When erythrocytes from 17 additional diabetics and 17 healthy controls were incubated for two hours at 37 degrees C in hyperglycaemic (50 mmol glucose/l) buffer, however, there was a considerable reduction in erythrocyte filterability for both diabetics and controls in parallel with an increase in erythrocyte sorbitol concentration. This loss of filterability was prevented by the addition of an aldose reductase inhibitor (Sorbinil). High glucose concentrations (congruent to 50 mmol/l) impair the filterability of erythrocytes through 3 micron pores, and the intracellular accumulation of sorbitol in poorly controlled outpatients is therefore unlikely to have a major adverse effect on erythrocyte rheology in diabetes mellitus.

Association of Motor Nerve Conduction Velocity with Fasting Plasma Glucose Levels and Erythrocyte Sorbitol Metabolism in Diabetic Neuropathy

Association of Motor Nerve Conduction Velocity with Fasting Plasma Glucose Levels and Erythrocyte Sorbitol Metabolism in Diabetic Neuropathy

Effects of sorbinil treatment on erythrocytes and platelets of persons with diabetes.

Thirty-three diabetic subjects were given the aldose reductase inhibitor sorbinil (Pfizer, UK) for 3 wk. There was a significant fall in mean erythrocyte sorbitol concentration over this period. In all subjects erythrocyte sorbitol concentrations after treatment were within or below the range found in normal subjects. No changes in erythrocyte 2,3-diphosphoglycerate (2,3-DPG) or myo-inositol concentrations, plasma beta-thromboglobulin (beta-TG) concentration, or P50--a measure of the oxygen affinity of hemoglobin--were observed. There was a high incidence of adverse reactions to the drug.

Effects of a fructose-rich diet and the aldose reductase inhibitor, ONO-2235, on the development of diabetic neuropathy in streptozotocin-treated rats.

Streptozotocin-diabetic rats were maintained on a 72% fructose diet for 4 weeks and some were treated with an aldose reductase inhibitor (either alrestatin: 0.9 g . kg-1 . day-1 or ONO-2235: 50 mg . kg-1 . day-1). Fructose feeding significantly influenced the development of impaired motor nerve conduction velocity in the diabetic rats and this effect was positively correlated with sorbitol accumulation in the sciatic nerve of diabetic rats maintained on a fructose-rich diet. Treatment with ONO-2235, a new aldose reductase inhibitor, prevented both slowing of motor nerve conduction velocity and elevation of nerve sorbitol concentration. On the other hand, erythrocyte sorbitol levels were significantly correlated to those of the sciatic nerve (r = 0.86, p less than 0.001) and the retina (r = 0.91, p less than 0.001) in these animals. Thus, our findings suggest that increased polyol pathway activity may be related to the pathogenesis of diabetic neuropathy and erythrocyte sorbitol concentrations may prove a useful indicator for the presence of diabetic complications.

Erythrocyte sorbitol dehydrogenase of selected non-mammalian vertebrates

1. 1. Erythrocyte sorbitol dehydrogenase activity (EC 1.1.1.14) from selected non-mammalian vertebrates was studied showing great variability not related to their phylogenetical position. 2. 2. The Michaelis-Menten constant ( K m) for sorbitol exhibited moderate low values in the studied animals. 3. 3. In snakes the K m for sorbitol was low with moderate activity of sorbitol dehydrogenase, suggesting that the enzyme could reach maximum activity with lower sorbitol concentration in comparison to other vertebrates. 4. 4. In the snakes the enzyme showed the same affinity for all the studied polyols, indicating that we are probably dealing with a very ancient enzyme, an unspecific enzyme.

Sorbitol accumulation is altered in type 1 (insulin-dependent) diabetes mellitus.

Intracellular sorbitol accumulation has been implicated as an aetiological factor for many of the complications of diabetes mellitus. Erythrocyte sorbitol is found in higher concentration in Type 1 (insulin-dependent) diabetic patients than in normal subjects. When sorbitol accumulation is corrected for its immediate precursor glucose (sorbitol/glucose ratio), the polyol accumulation remains significantly greater in erythrocytes from the Type 1 diabetic. Erythrocytes from Type 1 diabetic patients exposed to normal extracellular glucose concentrations for 3 h in vitro, accumulate more sorbitol and fructose than normal cells in the same incubation system. Near-normalization of plasma glucose in Type 1 diabetic patients for 12 h did not result in normal erythrocyte sorbitol levels. The increased sorbitol accumulation in erythrocytes from Type 1 diabetic subjects may reflect similar activity in the lens and nerve in long-standing diabetes. This increased sorbitol production was found in most, but not all, individuals with diabetes and appears to be an acquired characteristic. Those factors influencing enhanced tissue sorbitol accumulation may be important in the aetiology of diabetes-associated complications.

Determination of sorbitol in erythrocytes of diabetic and healthy subjects by capillary gas chromatography

A gas-liquid Chromatographie method, using a fused silica capillary column, for the determination of red cell sorbitol is described. The capillary column gives complete resolution of the polyols xylitol, inositol, mannitol, sorbitol and galactitol, even when the glucose peak in the red cell chromatogram is dominating. The identity of sorbitol, and its single elution from the capillary column has been confirmed by mass spectrometry. Recovery of sorbitol from various red cell samples was 101% ± 3.2 (mean ± SD, n = 7). Precision, estimated from duplicate diabetic red cell sorbitol analyses was CV dup = 3.5% ( n = 18) and from run to run analyses CV inlerassay = 4.0% ( n = 6). Sorbitol levels determined in erythrocytes of 19 healthy subjects were 5.9 ± 1.6 nmol/ml red cells and in erythrocytes of 18 insulin-dependent diabetics 17.8 ± 8.2 nmol/ml red cells (means ± SD). The method described offers a reliable and specific tool to study in vivo polyol pathway activity in relation to some diabetes-associated complications.

Role of red cell sorbitol as determinant of reduced erythrocyte filtrability in insulin-dependent diabetics.

Erythrocyte deformability measured as filtration index is clearly diminished in diabetics, thus possibly contributing to diabetes-associated microvascular complications. Moreover, the erythrocyte sorbitol level in IDD is clearly higher than that of non-diabetics, suggesting an alteration in the polyol pathway as possible determinant of diabetes-associated complications. Following this line of research, intracellular sorbitol as well as glucose, inositol, galactitol, mannitol and 2,3-diphosphoglycerate have been studied in 21 diabetics and in 14 controls matched for age and sex. In addition to confirming the high levels of intraerythrocytic glucose and sorbitol in diabetic subjects, statistically significant correlations have been demonstrated between sorbitol and filtration index, between plasma glucose, intracellular glucose level and glycosylated hemoglobin, suggesting a relationship between metabolic control and hemorheologic alterations in diabetes.

Sorbitol concentration in the plasma and erythrocytes of diabetic subjects.

Sorbitol content of plasma and red blood cells is increased in diabetic subjects, and it correlates with plasma glucose concentration. Rapid changes in plasma glucose concentration, either during normalization or impairment of glucose homeostasis, are paralleled by equally rapid changes in plasma or erythrocyte sorbitol content. At variance with a recent proposal, it is concluded that the measurement of sorbitol in red cells is not a reliable indicator of either long-term blood glucose levels or sorbitol accumulation in those tissues in which such an accumulation participates in the pathogenesis of degenerative complications.