"Polyol pathway"

Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway. During hyperglycaemia, some glucose bypasses glycolysis and is metabolised via the potentially neurotoxic polyol pathway, in which glucose is metabolised to sorbitol and fructose. Increased polyol concentrations have been demonstrated in the cerebrospinal fluid (CSF albumin ratio and preoperative cognitive function scores were significantly correlated with plasma glucose and CSF glucose, sorbitol and fructose levels. Hyperglycaemia causes a proportional increase in polyol concentrations in CSF of patients without major neurological disease. Furthermore, this study provides the first indication of upregulation of the cerebral polyol pathway in patients with diabetes

Effect of Resveratrol, a Dietary-Derived Polyphenol, on the Oxidative Stress and Polyol Pathway in the Lens of Rats with Streptozotocin-Induced Diabetes Resveratrol is found in grapes, apples, blueberries, mulberries, peanuts, pistachios, plums and red wine. Resveratrol has been shown to possess antioxidative activity and a variety of preventive effects in models of many diseases. The aim of the study was to investigate if this substance may counteract the oxidative stress and polyol pathway in the lens of diabetic rats. The study was conducted on the rats with streptozotocin-induced type 1 diabetes. After the administration of resveratrol (10 and 20 mg/kg for 4 weeks), the oxidative stress markers in the lens were evaluated: activity of superoxide dismutase, catalase and glutathione

Redox imbalance stress in diabetes mellitus: Role of the polyol pathway In diabetes mellitus, the polyol pathway is highly active and consumes approximately 30% glucose in the body. This pathway contains 2 reactions catalyzed by aldose reductase (AR) and sorbitol dehydrogenase, respectively. AR reduces glucose to sorbitol at the expense of NADPH, while sorbitol dehydrogenase converts sorbitol

Metabolomic Analysis Reveals Vitamin D-induced Decrease in Polyol Pathway and Subtle Modulation of Glycolysis in HEK293T Cells We combined H NMR metabolomics with functional and molecular biochemical assays to describe the metabolic changes elicited by vitamin D in HEK293T, an embryonic proliferative cell line adapted to high-glucose concentrations. Activation of the polyol pathway, was the most

Inhibitory Effect of Chemical Constituents Isolated from Artemisia iwayomogi on Polyol Pathway and Simultaneous Quantification of Major Bioactive Compounds Blocking the polyol pathway plays an important role preventing diabetic complications. Therefore, aldose reductase (AR) and advanced glycation endproducts (AGEs) formation has significant effect on diabetic complications. has long been used

Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer’s disease: metabolic basis for dementia Impairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer's disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites

Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral , but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway.

Polyol pathway mediates enhanced degradation of extracellular matrix via p38 MAPK activation in intervertebral disc of diabetic rats. The aim of this study was to determine the significance of diabetes on degradation of intervertebral disc (IVD) extracellular matrix. Diabetic rats showed a significant increase in glucose and sorbitol contents in the IVD. The levels of aldose reductase, p38 and metalloproteinases, and degradation of metalloproteinase-derived aggrecan and type II collagen were increased, while tissue inhibitors of metalloproteinases levels were decreased in the IVD of diabetic rats. These changes were markedly affected by inhibition of aldose reductase or p38. Diabetes might contribute to enhanced matrix degradation in the IVD and the polyol pathway might mediate this process via p38

polyol pathway, leading to degenerative neuropathy. The underlying mechanisms of sorbitol-induced degeneration have not been fully elucidated, and no current FDA-approved therapeutic options are available to reduce sorbitol levels in the nervous system. Here, in a Drosophila model of SORD deficiency, we showed synaptic degeneration in the brain, neurotransmission defect, locomotor impairment

Discovery of a novel benzothiadiazine-based selective aldose reductase inhibitor as potential therapy for diabetic peripheral neuropathy. Aldose reductase2 (ALR2), an activated enzyme in polyol pathway by hyperglycemia, has long been recognized as one of the most promising targets for diabetic complications especially in diabetic peripheral neuropathy (DPN). However, lots of ALR2 inhibitors

Fructose: A New Variable to Consider in SIADH and the Hyponatremia Associated With Long-Distance Running? Fructose has recently been proposed to stimulate vasopressin secretion in humans. Fructose-induced vasopressin secretion is not only postulated to result from ingestion of fructose-containing drinks, but may also occur from endogenous fructose production via activation of the polyol pathway

pathway is one of the primary mechanisms in the pathogenesis of diabetic complications, including development of DbCM. There is an unmet need for therapies targeting the underlying metabolic abnormalities that drive this form of Stage B heart failure (HF). Aldose reductase (AR) catalyzes the first and rate-limiting step in the polyol pathway, and AR inhibition has been shown to reduce diabetic Rationale and design of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure Trial (ARISE-HF) in patients with high-risk diabetic cardiomyopathy. Diabetic cardiomyopathy (DbCM) is a specific form of heart muscle disease that may result in substantial morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). Hyperactivation of the polyol

Inhibition of Aldose Reductase by Novel Phytocompounds: A Heuristic Approach to Treating Diabetic Retinopathy. Aldose reductase (ALR2) activation in the polyol pathway has been implicated as the primary mechanism for the progression of diabetic retinopathy. Most of the aldose reductase inhibitors (ARIs), used for the treatment of diabetic complications, were withdrawn due to ineffective treatment

Aldose reductase promotes diet-induced obesity via induction of senescence in subcutaneous adipose tissue. Aldose reductase (AKR1B1 in humans; Akr1b3 in mice), a key enzyme of the polyol pathway, mediates lipid accumulation in the murine heart and liver. The study objective was to explore potential roles for AKR1B1/Akr1b3 in the pathogenesis of obesity and its complications. The study employed

in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased

as a means for providing adequate fuel and water, while also providing protection from a decrease in oxygen availability. Fructose, whether supplied in the diet (primarily fruits and honey), or endogenously (via activation of the polyol pathway), preferentially shifts the organism towards the storing of fuel (fat, glycogen) that can be used to provide energy and water at a later date. Fructose causes

; GC-MS: R Y = 0.704, Q  = 0.444). Polyol pathways, myo-inositol, and oxidative stress seem to have a fundamental role in euploid and aneuploid pregnancies. Polyol pathways may have a crucial role in energy production in early pregnancy. Excessive activation in aneuploid pregnancies may lead to increased oxidative stress. Metabolomics represents a promising approach to investigate placental metabolic

Endogenous fructose production: what do we know and how relevant is it? Excessive sugar and particularly fructose consumption has been proposed to be a key player in the pathogenesis of metabolic syndrome and kidney disease in humans and animal models. However, besides its dietary source, fructose can be endogenously produced in the body from glucose via the activation of the polyol pathway . In this review, we aim to describe the most recent findings and current knowledge on the potential role of endogenous fructose production and metabolism in disease. Over the recent years, the activation of the polyol pathway and endogenous fructose production has been observed in multiple tissues including the liver, renal cortex, and hypothalamic areas of the brain. The activation occurs during

of the chemokine CCL2 through increased glycolysis and the polyol pathway. Furthermore, overexpression of GLUT1 in SMCs, but not in myeloid cells, accelerates development of larger, more advanced lesions in a mouse model of metabolic syndrome, which also exhibits elevated levels of circulating Ly6Chi monocytes expressing the CCL2 receptor CCR2. Accordingly, monocyte tracing experiments demonstrate that targeted