Galactose ingestion increases vascular permeability and collagen solubility in normal male rats.

Chang, Katherine; Tomlinson, Martha Scott; Jeffrey, J. R.; Tilton, Ronald G.; Sherman, William R.; Ackermann, Karen; Berger, Richard A.; Cicero, Theodore J.; Kilo, Charles; Williamson, Joseph R.

doi:10.1172/jci112821

Cited by 24 publications

(8 citation statements)

References 58 publications

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“…The increases in granulation tissue polyol levels and 125 Ialbumin permeation of granulation tissue vessels, as well as the decreased plasma levels of IGF-I, in sham-operated diabetic rats (vs. sham-operated nondiabetic rats) are consistent with previous observations in this animal model (20)(21)(22)(23)(24)28). The finding that granulation tissue polyol levels fell dramatically in 2-day insulin-pump diabetic rats and did not differ significantly from those of 2-day sham-operated control rats is consistent with the normalization of plasma glucose levels in these rats as well as with numerous reports demonstrating that the polyol content of cells and tissues is related to ambient glucose levels in vivo and that polyol levels increase during incubation of cells and tissues in vitro in media containing high concentrations of glucose (14)(15)(16)(35)(36)(37).…”

Section: Discussionsupporting

confidence: 91%

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Effect of Rapid Normalization of Plasma Glucose Levels on Microvascular Dysfunction and Polyol Metabolism in Diabetic Rats

et al. 1988

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Effects of rapid normalization of plasma glucose levels (by insulin infused via Alzet pumps implanted intraperitoneally) on plasma insulin-like growth factor I (IGF-I) levels, granulation tissue polyol levels, and vascular permeation by 125I-labeled albumin were examined in male Sprague-Dawley rats with streptozocin-induced (60-65 mg/kg) diabetes. Two days after implantation of pumps, plasma insulin levels were twice normal levels and remained elevated (1.4-2.5 times normal) throughout the remainder of the study. Plasma glucose levels and granulation tissue polyol levels were normalized within 2 days after initiation of insulin treatment. Plasma IGF-I levels were significantly increased (2 times) by 2 days, but were not normalized until 7 days. In contrast, 125I-albumin permeation normalized at a much slower relatively linear rate and was still not completely normal after 14 days of insulin treatment. In view of 1) previous studies demonstrating that diabetes-induced increases in 125I-albumin permeation in this tissue are linked to increased metabolism of glucose to sorbitol and 2) the rapid normalization of tissue polyol levels in this study, the relatively linear rate of normalization of vascular permeability over 14 days in these studies suggests that impaired vascular barrier functional integrity in this model is mediated by structural and/or functional vascular alterations associated with sustained increased polyol metabolism rather than by increased polyol levels per se and/or by readily reversible functional and metabolic alterations associated with acute increases in polyol metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 91%

“…Recently, increased polyol metabolism in diabetic animals has also been linked to the development of morphological (17)(18)(19) and functional (20)(21)(22)(23)(24)(25) changes in the microvasculature. The effect of rapid normalization of glycemia on polyol metabolism and vascular function in diabetic rats is unknown.…”

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confidence: 99%

Effect of Rapid Normalization of Plasma Glucose Levels on Microvascular Dysfunction and Polyol Metabolism in Diabetic Rats

et al. 1988

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“…Malmgren et al (19), Jakobsen et al (22), Sima and Robertson (23), and Powell et al (15) found no changes in bloodnerve barrier permeability to protein tracers such as albumin or horseradish peroxidase. On the other hand, increased blood-nerve barrier permeability in diabetic patients and diabetic and galactosemic animals has been reported by other investigators (20,21,(24)(25)(26). One possible reason for these conflicting results is that the change in blood-nerve barrier permeability of diabetic and galactosemic animals is subtle and difficult to detect with morphological techniques involving large protein tracers (27).…”

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confidence: 97%

Prevention of Nerve Edema and Increased Blood-Nerve Barrier Permeability–Surface Area Product in Galactosemic Rats by Aldose Reductase or Thromboxane Synthetase Inhibitors

et al. 1989

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Nerve water content and the permeability-surface area product (PA) to [3H]-or [14C]sucrose at the blood-nerve barrier were determined in unanesthetized control rats fed a normal diet and in rats fed galactose with or without an aldose reductase inhibitor (Statil or AL 1576) or a thromboxane synthetase inhibitor (CGS 12970). Nerve water content was determined by taking the difference between dry and wet weights of whole tibial nerves. PA was determined by an intravenous bolus injection of radiotracer with multiple-time-point graphic and quantitative autoradiographic methods. The mean nerve water content in galactosemic rats was 15% higher than in control rats after 7-11 mo on the diet. Statil and AL 1576 prevented nerve edema, but CGS 12970 was only partially effective in preventing an increase in nerve water content in galactose-fed rats. In galactosemic rats, the mean PA to sucrose at the blood-nerve barrier, calculated from nerve dry weight, was twofold higher than in control rats. Treatment with Statil, AL 1576, or CGS 12970 prevented increased PA. Our results suggest that nerve edema and increased blood-nerve barrier PA are secondary to polyol production and can be prevented by inhibiting aldose reductase.

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“…This could perhalps be related to a gradLual increcase in blood nerve barrier permeability (Chang, Tomlinson, Jeffrey, Tilton. Sherman, Ackeriman, Bergei, Cicero, Kilo & Williamson, 1987) allowing greater galactitol clearance. Fructose was slightly reduced in galactosaemic animnals, presumably because of competitioni by galactose reducing the flux of glucose through the polyol pathwxay.…”

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confidence: 99%

Muscle and nerve dysfunction in rats with experimental galactosaemia

Cameron¹,

Ma²,

Robertson³

et al. 1992

Experimental Physiology

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SUMMARYThe effects of up to 4 months dietary supplementation with 40 % galactose on muscle and nerve function were examined in rats. Galactitol, a polyol pathway metabolite, accumulated to high levels in both tissues. This led to changes similar to those found in experimental diabetes, which were largely prevented by treatment with an inhibitor of the first enzyme in the pathway, aldose reductase. For fast twitch extensor digitorum longus muscle there was weight loss, fibre damage, slowing of twitch time to peak, increased twitch tension, and reduced tetanic tension. There were no relaxation deficits. For slow twitch soleus there were no changes in tension production. However, contraction and relaxation for both twitch and tetanus were prolonged. Fatigue resistance was reduced after 1 week. Damage in soleus led to a reduction in mean fibre area after 2 months, which largely recovered by 4 months. There was a selective loss of fast oxidative glycolytic fibres. Histochemical staining for succinic dehydrogenase was normal in galactosaemic soleus, in contrast to the marked reduction seen in diabetes. Sciatic nerve conduction velocity was reduced after 2 months, particularly in normally fast conducting motor and sensory fibres. Resistance to hypoxic conduction block was increased in galactosaemic nerves to diabetic levels. It was concluded that polyol pathway hyperactivity is likely to contribute to the aetiology of diabetic myopathy and neuropathy, and that experimental galactosaemia provides a good model in which to study pathway effects without the complicated hormonal changes found in diabetes.

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Galactose ingestion increases vascular permeability and collagen solubility in normal male rats.

Cited by 24 publications

References 58 publications

Effect of Rapid Normalization of Plasma Glucose Levels on Microvascular Dysfunction and Polyol Metabolism in Diabetic Rats

Effect of Rapid Normalization of Plasma Glucose Levels on Microvascular Dysfunction and Polyol Metabolism in Diabetic Rats

Prevention of Nerve Edema and Increased Blood-Nerve Barrier Permeability–Surface Area Product in Galactosemic Rats by Aldose Reductase or Thromboxane Synthetase Inhibitors

Muscle and nerve dysfunction in rats with experimental galactosaemia

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