Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sorbitol, fructose, myo-inositol and lipid inositol concentrations were measured in excised dorsal root and sympathetic ganglia from rats with streptozotocin-induced diabetes, both in the acute stage (1 and 2 weeks after the induction of diabetes) and chronically (after 2 months of diabetes). In comparison with age-matched controls, myo-inositol concentrations were decreased by 26-32% after 1 and 2 weeks but had returned to normal levels at 2 months. Lipid inositol concentrations were normal both in the acutely and chronically diabetic animals. Sorbitol was not detectable in ganglia from diabetic or control animals except for a small quantity (0.05 mumol/g wet weight) in dorsal root ganglia at the 2-month stage. Fructose was present in dorsal root ganglia (1.71-3.53 mumol/g wet weight) at all stages and in sympathetic ganglia (2.18 mumol/g wet weight) at the 8-week stage. The differences in these results from those obtained in peripheral nerve trunks are possibly related to the lack of a blood-nerve barrier in sensory and autonomic ganglia.
 ...
PMID:Changes in sorbitol, myo-inositol and lipid inositol in dorsal root and sympathetic ganglia from streptozotocin-diabetic rats. 356 91

Total lipid, sucrose, glucose, sorbitol and myo-inositol contents in individual layers from normal and alloxan-diabetic rabbit retinas were measured using gravimetric and enzymatic microtechniques. Pure samples of nine retinal layers were microdissected from freeze-dried retinal cryosections. The lipid content was measured by loss of weight after ethanol and hexane extraction. Retinal lipid varied 3-fold across the retina and was not influenced by diabetes. Sucrose, glucose, sorbitol, and myo-inositol were measured with fluorimetric microassays. Sucrose infused intravenously prior to sampling the tissue did not traverse the outer blood retinal barrier of the normal or the diabetic retina. In both normals and diabetics, glucose followed a diffusional curve, with outer and inner retinal concentrations, respectively, equal to choroidal blood and vitreal glucose concentrations. Sorbitol was elevated in all retinal layers of diabetic animals. The peak sorbitol concentrations, of 2 mmol/kg defatted dry weight in diabetics, were not high enough to be osmotically significant. Retinal myo-inositol, of the order found in brain tissue (10-30 mmol/kg defatted dry tissue), was decreased by 22-40% in all retinal layers of the diabetics. The results indicate that diabetes affects the metabolism of retinal structures independently of the small blood vessel disease that is the hallmark of diabetes of long duration. It is conceivable that primary intraretinal metabolic alterations cause, aggravate, or perpetuate the well known degenerative processes that occur in retinal blood vessels in diabetes.
 ...
PMID:Altered retinal metabolism in diabetes. I. Microanalysis of lipid, glucose, sorbitol, and myo-inositol in the choroid and in the individual layers of the rabbit retina. 394 2

The rapid conversion of glucose to sorbitol by aldose reductase and the consequent hyperosmolarity of the cytoplasm has been shown to be the primary cause of the so-called "sugar" or "osmotic" cataract in many animal lenses. It is not as clear, however, that hyperosmolarity is the principal factor in the etiology of cataracts in human diabetic subjects. In fact, the comparatively low activity of aldose reductase in the human lens as compared with several animal lenses, and the osmotically insignificant levels of sorbitol pathway products (sorbitol and fructose), suggest that hyperosmolarity, per se, may not be as important a factor in human cataract formation as it is in animals. We present evidence that the flux of glucose and sorbitol through the rat lens is markedly reduced by oxidative stress (0.1 mM H2O2). Sorbitol accumulation is reduced by 114%, sorbitol turnover is reduced by 78%, sorbitol production is reduced by 90%, fructose accumulation is reduced by 60%, and fructose turnover is reduced by 76% in the presence of 36 mM glucose. H2O2 does not affect glucose turnover, the glucose rate constant, or the ATP level significantly at 36 mM glucose, but at 5.5 mM glucose, 0.2 mM H2O2 leads to a rapid loss of ATP that can be prevented by 0.04 mM sorbinil, an aldose reductase inhibitor. These results suggest that inhibition of aldose reductase by sorbinil renders rat lenses better able to cope with oxidative stress. In the absence of an aldose reductase inhibitor, elevating ambient glucose may render a lens less able to scavenge oxidants by diverting NADPH into sorbitol production.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Apr
PMID:The effect of oxidation on sorbitol pathway kinetics. 395 80

This investigation was designed to determine whether the aldose reductase inhibitor Sorbinil prevented the development of or reversed defects of nerve conduction and axonal transport in streptozotocin-diabetic rats. Untreated diabetes of either 3 or 6 wk duration caused a fall in sciatic motor nerve conduction velocity (MNCV) of 6-9 m/s (P less than 0.001) and significantly reduced the accumulation of axonally transported choline acetyltransferase activity against a 24-h sciatic nerve crush. These functional defects were associated with accumulation of sorbitol and depletion of myo-inositol in the sciatic nerve. Treatment with Sorbinil (25 mg/kg/day, p.o.) throughout the period of diabetes prevented the development of all these abnormalities in both 3- and 6-wk diabetic groups. In a second study, three groups of rats were subject to 3 wk untreated diabetes followed by Sorbinil treatment (as above) for 1, 2, or 3 wk to determine whether the abnormalities expected from 3 wk of untreated diabetes could be reversed. One week of treatment significantly elevated both MNCV and choline acetyltransferase accumulation (P less than 0.05). The longer treatments progressively ameliorated these defects such that the group that received Sorbinil for the second 3 wk of a 6-wk diabetic period gave values that were similar to controls and to diabetic rats that had been given Sorbinil throughout their diabetes. Sorbitol accumulation was markedly reduced by only 1 wk of Sorbinil treatment, but the normalization of myo-inositol levels required 2 wk of treatment. These findings indicate that Sorbinil treatment in diabetic rats prevented and reversed both Sorbitol accumulation and depletion of nerve myo-inositol in the sciatic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 May
PMID:Prevention and reversal of defective axonal transport and motor nerve conduction velocity in rats with experimental diabetes by treatment with the aldose reductase inhibitor Sorbinil. 620 76

Tissues of the eye affected by diabetes are the lens, cornea, and retina. The lens becomes cataractous through osmotic swelling of its cortical fibers. Sorbitol, formed in the presence of aldose reductase, accumulates in the lens during hyperglycemia. Dulcitol similarly accumulates in the presence of galactosemia. Cataractogenesis in both cases can be prevented by inhibitors of aldose reductase. The efficacy of synthetic inhibitors differs in various tissues and species, but they react with aldose reductase at a common structural site. The most promising inhibitor is sorbinil . Diabetic retinopathy is similarly related to sorbitol accumulation and may be prevented or reversed by inhibition of aldose reductase. Healing of corneal wounds in diabetes is facilitated by enzyme inhibition. Retinal vasculopathy of diabetes is due to selective loss of the intramural pericytes that normally form structural elements in the retinal capillary walls. The vulnerability of these cells is due to their aldose reductase content. Whether inhibition of aldose reductase will prevent retinopathy is being tested in a randomized trial conducted by the National Eye Institute.
 ...
PMID:NIH conference. Aldose reductase and complications of diabetes. 620 54

A gas-liquid chromatographic 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 CVdup = 3.5% (n = 18) and from run to run analyses CVinterassay = 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.
 ...
PMID:Determination of sorbitol in erythrocytes of diabetic and healthy subjects by capillary gas chromatography. 661 65

The effect of four kinds dietetic fruit products, sweetened by Sorbitol (pectin nectar, apricot nectar, apple and strawberry jam) on blood sugar and insulin needs of the patients was studied in 40 patients with insulin-dependent diabetes. The results were compared with those, obtained with the consumption of similar fruit products, sweetened by industrial sugar. The study was performed by an apparatus for automatic regulation of blood sugar (artificial endocrine pancreas--Biostator), which supplies the organism of the patients, overloaded with the respective product, with insulin, depending on the degree of glycemia and guarantees "normal" utilization of the product. The results obtained reveal that the blood sugar is slightly increased with the dietetic products, the peak of the blood sugar curve is lower and less insulin is supplied automatically by the biostator during the loading with the product. All values are lower, with a statistical significance, for the dietetic products as compared with the non-dietetic ones (p less than 0.05 to 0.001). Those data provide grounds to recommend the products studied as proper to be included in the diet of the diabetic patients.
 ...
PMID:[Effect of dietetic fruit products prepared with sorbitol and pectin on the blood sugar and insulin levels in diabetic patients]. 676 63

In 43 patients osmotherapy with Mannitol 20% and Sorbitol 40% was applied and the changes of the concentrations of lactate and pyruvate were tested in blood. The lactate level of both substances was increased. Sorbitol had the greater effect, and showed its maximum after one hour. For Mannitol the point effect was after four hours. Meanwhile Sorbitol produces an acidosis, the acid-base metabolism is unaffected after Mannitol. The pyruvate-level is not increased significantly, compared with the control group. Therefore the coefficient of lactate to pyruvate is significantly raised. These results highlight the problems of osmotherapy, if the changes of metabolism, induced by the therapy, are not considered. Lactid acidosis, previously existing or a general acidosis, shock, diabetes mellitus and hepatic dysfunctions enhance the risk of osmotherapy especially with Sorbitol.
 ...
PMID:[Blood-level changes of lactate and pyruvate after osmotherapy with mannitol and sorbitol (author's transl)]. 677 22

Three groups (6 patients with liver cirrhosis, 6 patients with diabetes mellitus, 6 controls) have been infused for 48 h with a 20% (w/v) glucose/sorbitol-solution (1:1). The only group where the infusion rate of 0,25 g carbohydrates/kg/h could not be reached was the control group with 0,232 g carbohydrates/kg/h. We could not see any significant changes in blood glucose levels during the total infusion period. Sorbitol levels dropped very slowly after the end of the infusion, a time when sorbitol was still excreted in the urine. The concentration of triglycerides was steadily increasing. Besides there were no further changes compared to equicaloric glucose or glucose/fructose infusions.
 ...
PMID:[Carbohydrate infusions in internal diseases. A comparative study in metabolically normal subjects, patients with liver diseases and diabetics. V. Infusion of a glucose-sorbitol mixture (ratio 1:1) for 48 hours]. 707 89

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.
Diabetes Care
PMID:Sorbitol concentration in the plasma and erythrocytes of diabetic subjects. 717 1


<< Previous 1 2 3 4 5 6 7 Next >>