Polyol pathway activity in nervous tissues of diabetic and galactose-fed rats: Effect of dietary galactose withdrawal or tolrestat intervention therapy

Sredy, Janet; Sawicki, Diane R.; Notvest, Ronald R.

doi:10.1016/0891-6632(91)90010-m

Cited by 25 publications

(14 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, in addition to cerebrovascular changes other factors, such as aberrant glucose metabolism in glia and neurones, are likely to affect the brain. Notably, increased glucose concentrations in the brain of STZ-diabetic rats were found to be associated with oxidative damage [52] and accumulation of sorbitol, fructose and advanced glycation end products [53,54,55], albeit to a lesser extent than in peripheral nerves. These metabolic changes are paralleled by a reduction in Na + , K + -ATPase activity in brain homogenates [56], which could account for a part of the reduced energy consumption in the brain of diabetic rats [14].…”

Section: Discussionmentioning

confidence: 99%

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

et al. 2001

View full text Add to dashboard Cite

It is becoming increasingly clear that the brain is another site of diabetic end-organ damage [1]. Some diabetic patients develop cognitive deficits, which are generally moderate in young adults [2] but can be more pronounced in the elderly [3]. Recent epidemiological studies even report an association between diabetes and dementia [3,4]. Given the prevalence of diabetes among the elderly and the effect of cognitive impairment and dementia on the quality of life of patients and health care resources, a better understanding of the effects of diabetes on the brain is needed.Experimentally diabetic rodents develop cerebral deficits similar to those observed in diabetic patients. Streptozotocin (STZ)-diabetic rats have been found to have impaired learning and memory functions [5] and increases in the peak latencies of brainstem audi- Diabetologia (2001) Abstract Aims/hypothesis. It is increasingly evident that the brain is another site of diabetic end-organ damage. The pathogenesis has not been fully explained, but seems to involve an interplay between aberrant glucose metabolism and vascular changes. Vascular changes, such as deficits in cerebral blood flow, could compromise cerebral energy metabolism. We therefore examined cerebral metabolism in streptozotocin-diabetic rats in vivo by means of localised 31 P and 1 H magnetic resonance spectroscopy. Methods. Rats were examined 2 weeks and 4 and 8 months after diabetes induction. A non-diabetic group was examined at baseline and after 8 months.Results. In 31 P spectra the phosphocreatine:ATP, phosphocreatine:inorganic phosphate and ATP:inorganic phosphate ratios and intracellular pH in diabetic rats were similar to controls at all time points. In 1 H spectra a lactate resonance was detected as frequently in controls as in diabetic rats. Compared with baseline and 8-month controls 1 H spectra did, however, show a statistically significant decrease in N-acetylaspartate:total creatine (±14 % and ±23 %) and Nacetylaspartate:choline (±21 % and ±17 %) ratios after 2 weeks and 8 months of diabetes, respectively. Conclusion/interpretation. No statistically significant alterations in cerebral energy metabolism were observed after up to 8 months of streptozotocin-diabetes. These findings indicate that cerebral blood flow disturbances in diabetic rats do not compromise the energy status of the brain to a level detectable by magnetic resonance spectroscopy. Reductions in Nacetylaspartate levels in the brain of STZ-diabetic rats were shown by 1 H spectroscopy, which could present a marker for early metabolic or functional abnormalities in cerebral neurones in diabetes. [Diabetologia (2001) 44: 346±353]

show abstract

Section: Discussionmentioning

confidence: 99%

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Increased reducing sugar in the serum of these animals has been demonstrated to be galactose (12,40). Galactose feeding has been demonstrated to cause tissue accumulation of galactose and its metabolites (2,12,26,37,40). Similarly to diabetes, galactose feeding has been shown to cause activation of PKC, MAPK, and PI3K-AKT, produce lipid peroxidation and oxidative stress, and lead to increased ECM protein production (5, 26, 30, 46).…”

Section: Discussionmentioning

confidence: 99%

Akt activation and augmented fibronectin production in hyperhexosemia

Xin¹,

Chen²,

Khan³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Dysmetabolic state in diabetes may lead to augmented synthesis of extracellular matrix (ECM) proteins. In the endothelial cells, we have previously demonstrated that glucose-induced fibronectin (FN) production and that of its splice variant, EDB+FN, is regulated by protein kinase B (PKB, also known as Akt). In this study, we investigated the role of Akt1 in ECM protein production in the organs affected by chronic diabetic complications. We studied Akt1/PKBα knockout mice and wild-type control littermates. To avoid confounding effects of systemic insulin, we used 30% galactose feeding to induce hyperhexosemia for 8 wk starting at 6 wk of age. We investigated FN mRNA, EDB+FN mRNA, and transforming growth factor (TGF)-β mRNA expression, Akt phosphorylation, Akt kinase activity, and NF-κB and AP-1 activation in the retina, heart, and kidney. Renal and cardiac tissues were histologically examined. Galactose feeding caused significant upregulation of FN, EDB+FN, and TGF-β in all tissues. FN protein levels paralleled mRNA. Such upregulation were prevented in Akt1-deficient galactose-fed mice. Galactose feeding caused ECM protein deposition in the glomeruli and in the myocardium, which was prevented in the Akt knockout mice. NF-κB and AP-1 activation was pronounced in galactose-fed wild-type mice and prevented in the galactose-fed Akt1/PKBα-deficient group. In the retina and kidney, Ser473 was the predominant site for Akt phosphorylation, whereas in the heart it was Thr308. Parallel experiment in streptozotocin-induced diabetic animals showed similar results. The data from this study indicate that hyperhexosemia-induced Akt/PKB activation may be an important mechanism leading to NF-κB and AP-1 activation and increased ECM protein synthesis in the organs affected by chronic diabetic complications.

show abstract

“…Brain tissues may be subject to nonenzymatic glycosyl-ation (209). The brain seems to be less affected by polyol metabolic abnormalities via the aldose reductase pathway than other tissues (210,211). It is possible that selective CNS cells are impaired, however (212).…”

Section: A Chronic Diabetic Encephalopathymentioning

confidence: 99%

The Impact of Diabetes on the CNS

McCall

1992

Diabetes

254

View full text Add to dashboard Cite

The brain is not usually thought to be a target of chronic diabetes complications. Nonetheless, substantial evidence, summarized herein, suggests that diabetes causes brain damage. Clinical syndromes of diabetes-related brain abnormalities are discussed along with possible causes. Various physiological effects of diabetes are reviewed, and questions are raised about gaps in our knowledge. Appropriate directions for future research are suggested.

show abstract

Polyol pathway activity in nervous tissues of diabetic and galactose-fed rats: Effect of dietary galactose withdrawal or tolrestat intervention therapy

Cited by 25 publications

References 35 publications

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

Akt activation and augmented fibronectin production in hyperhexosemia

The Impact of Diabetes on the CNS

Contact Info

Product

Resources

About