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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent advances in nutritional and biochemical research have substantiated the importance of inositol as a dietary and cellular constituent. The processes involved in the metabolism of inositol and its derivatives in mammalian tissues have been characterized both in vivo and at the enzyme level. Biochemical functions elucidated for phosphatidylinositol in biological membranes include the mediation of cellular responses to external stimuli, nerve transmission, and the regulation of enzyme activity through specific interactions with various proteins. Inositol deficiency in animals has been shown to produce an accumulation of triglyceride in liver, intestinal lipodystrophy, and other abnormalities. The metabolic mechanisms giving rise to these latter phenomena have been extensively studied as a function of dietary inositol. Altered metabolism of inositol has been documented in patients with diabetes mellitus, chronic renal failure, galactosemia, and multiple sclerosis. A moderate increase in plasma and nerve inositol levels by dietary supplementation has been suggested as a means of treating diabetic neuropathy, although excessively high levels, such as are found in uremic patients, may be neurotoxic. A thorough consideration of the biochemical functions of inositol and a further characterization of various diseases with the aid of appropriate animal models may suggest a possible role for inositol and other dietary components in their prevention and treatment
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PMID:The nutritional significance, metabolism, and function of myo-inositol and phosphatidylinositol in health and disease. 627 2

A variety of agents are currently available that claim to either prevent, delay, or reverse cataracts associated with aging (senile cataracts), radiation, or diabetes and galactosemia (sugar cataracts). Senile cataract therapy includes formulation containing inorganic salts, nutritional supplements, natural product extracts, sulfhydryl, and sulfonic acid containing compounds and miscellaneous redox and nonsteroidal anti-inflammatory compounds. Agents associated with the treatment of radiation cataracts include anti oxidants and free radial scavengers. Aldose reductase inhibitors have been effective in the prevention of sugar cataracts. A summary of these agents and their potential ocular effects are presented.
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PMID:Overview of the current attempts toward the medical treatment of cataract. 634 28

Six normal dogs were made galactosemic by feeding a 30% D-galactose diet, and were followed up to 5 yr. For comparison, 10 normal dogs and 10 alloxan-diabetic dogs were concurrently fed the diet less the galactose supplement. Retinopathy occurred in each of four dogs glactosemic 3 or more yr, and was absent at lesser durations of galactosemia, and from normal dogs not given the galactose supplement. The retinopathy was marked by saccular capillary aneurysms, hemorrhages, nonperfused or acellular vessels, tortuous hypertrophic capillaries, loss of capillary pericytes, and other lesions typical of diabetic patients and alloxan-diabetic dogs. In galactose-fed dogs, blood galactose varied between 0 (fasted) and 250 mg/dl (postprandial), and glycosylated hemoglobin levels became supranormal. In contrast to diabetic dogs, blood levels of glucose, free fatty acids, and branched-chain amino acids were not elevated in the galactosemic dogs, and their serum insulin seemed normal. The results suggest that the level of blood hexose is itself an important determinant of retinopathy.
Diabetes 1984 Jan
PMID:Experimental galactosemia produces diabetic-like retinopathy. 636 Jul 71

Two patients with idiopathic Fanconi syndrome and glucose intolerance were studied from a metabolic perspective. They had fasting hyperglycemia, massive glucosuria, insulinopenia, ketosis, and elevated serum free fatty acids. There was a markedly blunted insulin secretory response to glucagon, tolbutamide, glucose, and arginine. One patient had the findings of diabetic retinopathy and a sensory neuropathy. Neither patient could convert galactose to glucose, but they did not have galactosemia. As a result of these studies, and previous reports in which similar changes were noted, we conclude that diabetes mellitus may occur in patients who have had idiopathic Fanconi syndrome for many years.
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PMID:Metabolic abnormalities in the idiopathic Fanconi syndrome: studies of carbohydrate metabolism in two patients. 701 70

Diabetes mellitus is a disease that affects multiple organ systems. In our laboratory it has been shown that there is a significant loss of outer hair cells in genetically diabetic rats. Galactosemia can also produce diabetic-like changes. This study was performed to demonstrate whether these changes also occur in the cochlea. Three groups of Sprague-Dawley rats were used and fed either a control diet, a 50% galactose diet, or a 50% galactose diet with the addition of an aldose reductase inhibitor. After 6 months the animals were killed, and the cochleas were removed, fixed, and stained. Diabetes-induced damage was assessed by counting the hair cells and calculating the neuroganglion cell density. The histopathologic changes induced by galactose were manifested as outer hair cell loss and a decrease in neuroganglion cell density. Control animals had the least amount of hair cell loss and the greatest neuroganglion cell density of all three groups. Galactose-only animals demonstrated the most pronounced changes in both hair cell loss and neuroganglion cell degeneration; however, only changes of neuroganglion cell density in the basal turn were significant. The addition of an aldose reductase inhibitor provided inconclusive results in both hair cell determination and neuroganglion cell density; however, generally the inhibitor partially prevented the damage produced by galactose. These results suggest that a high-galactose diet can induce diabetic-like changes in the cochlea.
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PMID:Consumption of a high-galactose diet induces diabetic-like changes in the inner ear. 750 87

Microaneurysms, acellular capillaries and pericyte ghosts are characteristic of diabetic retinopathy, but it is not clear what causes these lesions or whether they are causally related to each other. The distribution of microaneurysms, acellular capillaries and pericyte ghosts has been evaluated in two animal models of diabetic retinopathy, diabetic dogs (n = 25) and galactose-fed dogs (n = 12). After 5 years of diabetes or galactosemia, retinas were divided into four quadrants at the optic disk, prepared by the trypsin-digest method, and the frequency of the lesions compared among the quadrants. Numbers of lesions were expressed relative to area of trypsin-digested retina examined or to total number of capillary cells examined. Microaneurysms and acellular capillaries were not uniformly distributed across the retina in diabetes or in galactosemia, both lesions being significantly (more than two-fold) more prevalent in the superior temporal retina than in the inferior nasal quadrant of retina. In contrast, the distribution of pericyte ghosts in these same eyes was not significantly different between the quadrants. These findings suggest that pericyte loss may not be sufficient to account for the development of microaneurysms and acellular (occluded) capillaries in diabetes, and raise a possibility that the lesions occur by different mechanisms. Currently available hypotheses regarding the pathogenesis of diabetic retinopathy fail to account for regional differences in the distribution of the vascular lesions within the same retina. Local factors within the eye apparently play an important role in the response of the retinal microvasculature to hyperglycemia.
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PMID:Vascular lesions in diabetes are distributed non-uniformly within the retina. 761 20

Cellular accumulation of galactitol has been suggested to cause the apparent dietary-independent, long-term complications in classic galactosemia. Experimental animals rendered hypergalactosemic by galactose feeding accumulate tissue galactitol, as well as millimolar quantities of galactose, and manifest biochemical, physiological and pathological abnormalities which are generally eliminated or curtailed by the concomitant administration of an aldose reductase inhibitor. This includes reduced cellular content of the cyclic polyol, myo-inositol, which like galactitol may function as an alternate intracellular osmolyte. However, the abnormalities detected in experimental galactosemic animals are more compatible with findings in experimental diabetes mellitus than in human galactosemia. Because patients with galactokinase deficiency fail to manifest the CNS and ovarian complications which characterize classic galactosemia, yet during long-term lactose restriction excrete comparable urinary quantities of galactitol, this polyol alone is not likely to play an important role during postnatal life in the pathogenesis of long-term complications. Notwithstanding, a role for either galactitol or myo-inositol in an intrauterine toxicity cannot be dismissed.
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PMID:The role of polyols in the pathophysiology of hypergalactosemia. 767 66

Galactose-fed rats develop a retinal microvascular disease, but retinopathy has not been found to develop reproducibly in diabetic rats. We sought to determine which retinal lesions can be reproducibly produced by long-term diabetes in rats, the extent to which the capillary lesions in diabetic rats and galactosemic rats are similar, and whether the retinopathy induced by 50% galactose can be reproduced satisfactorily by a lower concentration of galactose. Alloxan-diabetic rats and rats fed either a 50% galactose diet or a 30% galactose diet were killed after comparable durations of study (18 to 22 months). Rats fed 50% galactose showed greater than normal frequency of retinal pericyte ghosts and acellular capillaries, and thickening of capillary basement membranes by 18 months of galactosemia. Rats eating 30% galactose developed similar retinal lesions, and tended to be healthier than rats fed 50% galactose. Diabetes of 1 1/4 years or more likewise resulted in retinal pericyte ghosts, acellular capillaries and thickened capillary basement membrane. IRMAs and other vascular abnormalities were not reproducibly demonstrated at this duration of study, and saccular microaneurysms were not seen in any groups. In a number of diabetic rats, the severity of diabetes diminished spontaneously (after 1 to 1 1/2 years of insulin deficiency), thus making it essential that glycemia be systematically monitored. Both diabetic rats and experimentally galactosemic rats develop microvascular lesions that are consistent with at least the early stages of diabetic retinopathy, and these models should be useful to screen potential therapies for their ability to inhibit the development of retinopathy.
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PMID:Comparison of retinal lesions in alloxan-diabetic rats and galactose-fed rats. 772 Mar 92

Levels of the intracellular antioxidant, glutathione, become subnormal in retina in diabetes or experimental galactosemia. In order to investigate the cause and significance of this abnormality, activity of gamma-glutamyl transpeptidase (an enzyme important in the synthesis and degradation of glutathione) and levels of reduced glutathione have been measured in retinas of diabetic rats and dogs and of experimentally galactosemic rats and dogs. Retinal gamma-glutamyl transpeptidase activity and glutathione level were significantly less than normal after 2 months of diabetes or galactosemia. In contrast, cerebral cortex from the same diabetic rats and galactosemic rats showed no significant reduction in either gamma-glutamyl transpeptidase activity or glutathione level. These different responses of the two tissues to hyperglycemia might help account for the difference in microvascular disease in these two tissues in diabetes. Consumption of the antioxidants, ascorbic acid (1.0%) plus alpha-tocopherol (0.1%), by diabetic rats and galactosemic rats inhibited the decrease of gamma-glutamyl transpeptidase activity and glutathione levels in retina, suggesting that defects in glutathione regulation in the retina are secondary to hyperglycemia-induced 'oxidative stress'.
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PMID:Abnormalities of retinal metabolism in diabetes or galactosemia. II. Comparison of gamma-glutamyl transpeptidase in retina and cerebral cortex, and effects of antioxidant therapy. 772 Mar 97

The present study was designed to examine the development of structural changes, characteristic of diabetic neuropathy, in chronic galactosemia and their responsiveness to inhibition of the polyol-pathway. Sprague-Dawley rats weighing 70-90 g were given a 50% galactose diet continued for 4 or 8 months. Half of these animals were simultaneously given the aldose reductase inhibitor (ARI) WAY 121-509. ARI-treatment normalized galactitol and myoinositol levels in the sciatic nerve. At 4 months, sciatic nerve conduction velocity (NCV) in galactosemic rats was reduced by 30% which was prevented in ARI-treated rats. At 8 months galactosemia reduced NCV to 58% of control values, while ARI-treatment for 8 months improved NCV to 71% of control values. ARI-treatment prevented in galactosemic rats nodal structural changes characteristic of diabetic neuropathy, whereas axonal atrophy was not affected by ARI-treatment, which may in part account for the only partial prevention of the NCV slowing at 8 months. Nerve fiber regeneration was increased 4-fold in ARI-treated rats compared with untreated galactosemic rats. These data suggest that chronic galactosemia produces a neuropathy structurally similar to diabetic neuropathy. The lack of an ARI-treatment effect on axonal atrophy suggests that this defect is not polyol related in galactosemia.
Diabetes Res Clin Pract 1994 Sep
PMID:Galactosemia produces ARI-preventable nodal changes similar to those of diabetic neuropathy. 782 Nov 91


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